Fred Lembeck

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Fred Lembeck (born July 4, 1922 in Herzogenburg-Oberhaben in Lower Austria ; † October 22, 2014 in Graz ) was an Austrian doctor and pharmacologist . He was best known for his discovery of serotonin in carcinoid tumors and substance P as a neurotransmitter of the afferent, sensory nerve fibers . In these areas he led research to the threshold of molecular biology .

Lembeck explains the pharmacology of serotonin in Graz in 1970

Life

Lembeck was one of two children of the locksmith Hartwig Lembeck and his wife Anna née Leinwater, a teacher by profession. Fred studied medicine in Vienna and Graz. The Second World War interrupted his studies. Lembeck was a soldier from 1941, most recently as a field doctor, and from 1945 to 1946 in American captivity. Dismissed, he worked alongside his studies at the war-damaged Physiological Institute of the University of Graz and after receiving his doctorate as Dr. med. univ. from October 28, 1947 at the pharmacological institute with Hans Häusler (1896–1970), also damaged by the war. He reports (from English): “Only the office for the professor and another room for everything else, including the breeding of rats, could be heated. We spent our time doing primitive activities like making copper-free distilled water and crystallizing sodium chloride to a purity that would not kill a frog's heart. I was desperately looking for a decent job for a young doctor. At that time a representative of the World Health Organization came to Graz. He was immediately taken to Professor Häusler, the faculty's only English-speaking professor. I am very grateful to Häusler that he persuaded the WHO representative to arrange for me a six-month scholarship with John Henry Gaddum in Edinburgh , although I had no experimental experience yet. My arrival there, a year after my doctorate in 1947, meant my entry into pharmacology. ”Back in Graz, he completed his habilitation on April 30, 1954 with his thesis on serotonin in carcinoids for pharmacology. From 1961 to 1969 he held the position of director of the Pharmacological Institute of the Eberhard Karls University of Tübingen and from 1969 to 1992 he held the position of director of the Institute of Pharmacology - renamed the Institute for Experimental and Clinical Pharmacology and Toxicology - of the University of Graz from 1969 to 1992 . In 1992 he retired. Since 1974 he lived in the Graz district of St. Peter , in whose cemetery near the parish church of St. Peter he is buried. He left two sons and a daughter. His successor at the Graz chair was Bernhard Alfred Peskar (* 1941) in 1994.

research

Throughout his life, Lembeck was fascinated by the chemical signals that organs and cells use to communicate with one another, be it the signals from endocrine glands , i.e. the hormones, or the signals from nerve cells, i.e. the neurotransmitters . Besides Gaddum, he had three great role models as a researcher. One of them was Otto Loewi , who in Graz in 1921 discovered the chemical transmission of information from the vagus nerve and the sympathetic nerve to the heart (from frogs) and thus the principle of chemical neurotransmission in general, and who a little later identified acetylcholine as the transmitter of the vagus nerve. The second role model was Henry Hallett Dale , who found histamine in animal tissue with George Barger (1878–1939) in 1910, also examined the effects of adrenaline and noradrenaline in 1910 and anticipated noradrenaline as a transmitter of the postganglionic sympathetic nerves, in 1906 the existence of several receptors for Discovered adrenaline and in 1933 introduced the classification of neurons according to their transmitter - for example as "cholinergic" and "adrenergic". The third was Wilhelm Feldberg , who at Dales National Institute for Medical Research - partly together with Marthe Vogt , John Henry Gaddum and George Lindor Brown (1903–1971) - had detected acetylcholine as a transmitter of other neuron systems, such as the nerves of the skeletal muscles and some neurons in the brain. Lembeck honored the three scientists in his book with Josef Donnerer "The Chemical Languages ​​of the Nervous System". In her (and therefore his) research area, the chemical communication between cells and organs , " physiology and pharmacology join hands" according to his understanding, as Ernest Henry Starling put it . “The pharmacology parlor” was the name given by the staff at the neighboring Institute for Toxicology in Tübingen with ironic recognition .

  • role models

  • Otto Loewi at the Pharmacological Institute in Graz in the 1950s with a kymograph

  • Wilhelm Feldberg, Henry Hallet Dale and John Henry Gaddum (from left) around 1960

Lembeck's first printed work stems from the intersection of physiology and pharmacology. In 1946, shortly before visiting Gaddum in Edinburgh, Ulf von Euler had identified norepinephrine as a postganglionic sympathetic transmitter, and the question arose as to whether norepinephrine was also released from the adrenal medulla as a companion to adrenaline . Gaddum and Lembeck's experiments on cats affirmed this, as did experiments by Joshua Harold Burn and Edith Bülbring in Oxford and by Peter Holtz and Hans-Joachim Schümann in Frankfurt am Main - the catecholamines were a prominent topic in those years.

Another practical consequence of Euler's discovery was that norepinephrine was tested as an additive to solutions of local anesthetics in order to prolong their effect and limit side effects. Lembeck made a contribution by comparing noradrenaline, adrenaline and α-methylnoradrenaline.

Serotonin in carcinoids

In Graz, the pathologist Max Ratzenhofer (1911–1992) confronted Lembeck with the problem of carcinoids, rarer, mostly benign tumors that mainly occur in the gastrointestinal tract and originate from the enterochromaffin cells . Both the origin of these cells and some symptoms of the disease - attacks of reddening of the face and neck and diarrhea - suggested that the tumors were releasing chemical signals. Identification efforts, such as by Ratzenhofer's predecessor Friedrich Feyrter , had failed. When a 65-year-old woman with a metastatic (i.e. malignant) small bowel carcinoid was autopsied in 1953, a new attempt was made.

Gaddum helped Lembeck in two ways. First, his time in Edinburgh had introduced him to bioassays , the identification and quantification of substances based on their effect on blood pressure or on isolated organs such as the uterus or pieces of the intestine. Secondly, Gaddum told him about the previously unknown serotonin that the Italian pharmacologist Vittorio Erspamer had just found in the enterochromaffin cells in 1952. Lembeck received 10 mg of serotonin from the USA. The metastases were extracted. In addition to chemical reactions and separation by paper chromatography, numerous bioassays followed - on the small intestine of guinea pigs, on the uterus and large intestine of rats, on the small intestine and the blood vessels of the ears of rabbits, on the blood pressure and the nictitating membrane of cats - with the result: "The investigation of carcinoid metastases resulted in a content of at least 2.5 mg / g 5-oxytryptamine <= serotonin>, in addition, a second intestinal substance could be detected. This confirmed Erspamer's view of the origin of 5-oxytryptamine from the enterochromaffin (yellow) cells of the digestive tract and supported Feyrter's thesis of its endocrine significance. ”Later, Lembeck saw the attention with which he had registered another signal besides serotonin that was particularly important . Today the carcinoids are counted among the neuroendocrine tumors . For example, they can release adrenaline, histamine, gastrin and vasoactive intestinal peptide as further chemical signals .

A follow-up study showed that in carcinoid patients the excretion of serotonin and its breakdown product 5-hydroxyindole acetic acid in the urine was increased.

Regarding the effect of serotonin on the intestine, the focus was initially on the smooth muscles . Lembeck, Karl-Friedrich Sewing (1933–2019) and Dietrich Winne (* 1930) in Tübingen also asked in 1966 about an influence on the fluid exchange in the intestine. “Such studies appear to be of particular interest with regard to the watery diarrhea associated with carcinoids. We therefore investigated the effect of serotonin on the absorption of tritium water (HTO) from the rat small intestine in situ . Serotonin led to a delay in water absorption in rats after intravenous as well as enteral administration. ”The publication requires the retrospective comment that more important than the inhibition of fluid absorption from the intestine is the promotion of fluid secretion into the intestine by serotonin Tübingen group later misunderstood. However, the group opened the topic "Serotonin and fluid movements in the intestine". It has become important. Lembeck's Graz employees later recognized, for example, that serotonin mediates the intestinal effects of cholera toxin and some laxatives .

Substance P - transmitter of sensitive nerve cells

The essay “On the question of the central transmission of afferent impulses. III. Message. The occurrence and importance of substance P in the dorsal roots of the spinal cord “is famous for its origin and content. It is rooted in Loewi's last investigations in Graz in 1938. Loewi and his assistant Kurt Hellauer (1913–2002) wanted to know whether acetylcholine would be a transmitter in afferent, sensitive nerve fibers, as in various efferents . However, the posterior nerve roots , in which the afferent fibers reach the spinal cord, were free of acetylcholine , unlike the anterior nerve roots , in which the efferent fibers exit the spinal cord. In the middle of experimenting, Loewi encountered National Socialist racism . He reports in his autobiography: “On March 11, 1938, I carried out an experiment with an assistant that was to be the last in a series that had all shown that afferent nerves, unlike efferents, had no trace of acetylcholine contain. In the late afternoon the assistant told me that the Nazis had just taken over the country. My mind was so focused on our latest finding that I missed the full meaning of this message! This almost unbelievable indifference continued when we heard Schuschnigg's farewell speech as Chancellor on the radio before going to bed . ”Loewi was arrested that night. Work in the Pharmacological Institute broke off. Loewi emigrated. One trace can be found in a footnote: "Examinations already in progress on possible adrenaline content of the post- and preganglionic fibers had to be temporarily interrupted for external reasons."

After the war - Loewi lived in New York - two scientists from Graz took up the topic again, Hellauer, who had completed his habilitation in physiology in 1944 and worked at the Physiological Institute, and Karl Umrath (1899–1985), who in 1931 specialized in plant and animal physiology and biophysics and worked at the Zoological Institute. The two started from the observation that "antidromic" stimulation of afferent nerve fibers - stimulation against the normal direction of conduction - triggers vasodilation in the peripheral area in which the fibers branch and from which they conduct signals centrally , "antidromic vasodilation". Hellauer and Umrath suspected that the peripheral branches released the same substance as the fibers entering the spinal cord, namely the transmitter - they wrote the "action substance" - of the afferent nerve cells. They tested whether extracts on the one hand from the ventral and on the other hand from the dorsal nerve roots mimicked the "antidromic vasodilation", namely had a vasodilatory effect when injected subcutaneously into the ears of rabbits, with the result: Only extracts from the dorsal roots had a strong and persistent effect: "Compared to the For non-sensitive, ventral roots of the spinal cord, the sensitive, dorsal roots provide an extract which, when injected subcutaneously, reddened the rabbit ear. ”The responsible substance was neither acetylcholine nor histamine. “So it must be a different, vasodilator chemical body with the properties of an action substance. That means that the substance acts as a transmitter at the nerve endings and is also otherwise present in the course of the nerve. ”The back roots also contained an enzyme that destroys the“ action substance ”. The occurrence of “action substance” and enzyme was examined more closely in a further work.

Lembeck calls his essay a “III. Message". There is no specifically so-called "I. Communication "or" II. Message". But Lembeck was undoubtedly thinking of the two 1948 publications by Hellauer and Umrath. So what was the “action substance”? Gaddum helped again - through his discovery 22 years ago (with von Euler) of a vasodilating substance in the brain and intestine of horses that contracted the smooth muscles of the intestine, the substance P. With this, Lembeck decided to compare the extracts from anterior and posterior roots . In 1953, Substance P was rather obscure. It appeared to be a peptide ; but was it even a single chemical compound? "Even if the previous findings did not give any indication of the effectiveness of substance P as a stimulant substance for any nerves, it appeared to be the only one of the substances that have been described and examined more closely." Contractions of the isolated ileum of guinea pigs proved proved to be a sensitive bioassay for substance P. Even with raw extracts, a clear difference was found between the anterior and posterior nerve roots of cattle; the anterior ones contained at most 1/10 of the posterior roots of substance P-like material. In all the properties investigated, the material from back roots corresponded to authentic substance P provided by Euler: in terms of solubility, stability to acids and bases, behavior during dialysis , precipitation from solutions, paper chromatography, enzymatic degradation and vasodilation in the Rabbit ear according to Hellauer and Umrath. The thesis concludes: "The evidence of substance P in the dorsal roots and its extensive similarity with the 'excitation substance of sensory nerves' make its importance as a transmitter of the first sensitive neuron appear possible."

Thirty years later a review article stated: “As early as 1953, substance P was proposed as a neurotransmitter in various areas of the central and peripheral nervous system. The primary afferent neurons were of particular interest. "In 2001, a verdict (taken from English) was:" In Austria, Fred Lembeck presented weighty arguments in his elegant pioneering work for substance P as a sensory neurotransmitter. "Today (2012) there is no doubt that that substance P is a - not the only - transmitter of the primarily afferent neurons, more precisely of the Aδ and C fibers serving for pain perception , and on top of that the transmitter of many other neurons in the intestinal nervous system and in the central nervous system. “Substance P has some priorities. It was discovered in the brain and intestines of horses in 1931, a double occurrence which, in retrospect, can be explained with its transmitter role here and there. In 1953 a much higher concentration was found in the posterior roots of the spinal cord than in the anterior roots and it was suggested that substance P could be a transmitter of the first sensory neuron. When the chemical analysis finally succeeded in 1971, substance P was the first 'pure' neuropeptide known in its structure, ' pure' to differentiate between intestinal hormones such as gastrin and pituitary hormones such as vasopressin , which are also neurotransmitters. ”Lembeck wrote his article from 1953, how all authors in volume 219 of Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology , “Prof. Dr. Dedicated to Otto Loewi on the occasion of his 80th birthday ”.

Further research on substance P

In the years after 1953, Lembeck's group, confirming earlier findings, detected substance P in the brains of various animal species , like other neurotransmitters in the presynaptic endings of nerve cells. Substance P increased the permeability of the blood vessel walls for liquids, so that when injected into the skin, plasma extravasation , i.e. plasma leakage, occurred and a wheal formed.

All these investigations were carried out with tissue extracts containing substance P, and even if “substance P” effects persisted after partial cleaning, such as the effect on blood vessel permeability, uncertainty remained.

At the end of the 1960s, Lembeck contributed to eliminating this uncertainty, namely to the pure representation and structure elucidation, but only indirectly. Vittorio Erspamer had found substance P-like peptides in unexpected places, namely in 1949 the eledoisin in the salivary gland of the musk octopus ( Eledone moschata ) and in 1962 in the skin of southern frog species of the genus Physalaemus the physalamin . Because of their common property of causing smooth muscles to contract faster - not too slower like bradykinin - he called them together with substance P tachykinins . Cross tolerance , i.e. a mutual weakening of the effect , also spoke in favor of similarities.

Eledoisin and Physalämin stimulated the flow of saliva, and they did so very strongly. The same thing had been observed with substance P. Lembeck decided to investigate the phenomenon more closely. All three substances increased the secretion of saliva in dogs, rats and chickens. The effect of the substance P preparations could be eliminated by proteolysis , as was required for a peptide . Antagonists at receptors for acetylcholine, noradrenaline and histamine did not weaken the effect. "Physalamin, eledoisin and substance P seem to intervene in the secretion mechanism at a point that is secondary or subordinate to the histamine and acetylcholine receptors."

In the course of these investigations, Lembeck came up with the idea with which he wrote himself in the history of structure elucidation (from English): “On May 4, 1967 < recte according to the newspaper date on May 24> I read the Frankfurter Allgemeine Zeitung in a comfortable InterCity . There was a brief message there, 'Saliva secreted by enzymes'. Leeman and Hammerschlag from Brandeis University had isolated a new hormone responsible for salivary flow from the hypothalamus , a protein, which they called 'sialogen'. I think I was the only reader fascinated by this note from an unknown journalist. After arriving in Tübingen, I sent Leeman our results by airmail. Samples were exchanged and it soon became clear that 'Sialogen' and substance P were identical. ”Likewise, Lembeck's colleague told Klaus Starke the story during these experiments . After contact with Lembeck, American scientists also found substance P and Sialogen to be “startlingly similar” - “terrifyingly similar”, and when Susan E. Leeman's group determined the structure in 1971, forty years after the discovery, it was the structure of the substance P, the neuropeptide with the longest research history. The name “Sialogen” has been abandoned, but substance P is, if not a salivary-promoting hormone, at least a salivary-promoting cotransmitter with acetylcholine in the salivary gland nerves.

After the structure elucidation

Thanks to structural elucidation, the availability of pure substance P and the methods of molecular genetics, research into tachykinins proliferated. In 1983 two more mammalian tachykinins were discovered, neurokinin A and neurokinin B , and in 1991 the two genes that code substance P and the two neurokinins. From the same years we learned about three tachykinin receptors in mammals, NK 1 , NK 2 and NK 3 , and about antagonists that block these receptors. In 1982 Lembeck's group in Graz showed that two peptide antagonists blocked the vasodilator and permeability-increasing effects of pure substance P - the pure substance had confirmed the findings with impure substance P preparations. In 1992 the group reported in detail for the first time on in vivo studies with a non-peptide antagonist, "CP-96,345". He also blocked vasodilation and plasma extravasation after injection of substance P. In addition, he blocked contractions of the intestinal muscles using substance P and a bronchoconstriction triggered by substance P , but also had effects on the heart that were independent of neurokinin receptors.

Capsaicin

Already a decade earlier, an apparently remote substance had threaded into substance P research. Capsaicin is primarily responsible for the burning pungent taste of paprika , the feeling of warmth when consumed or applied to the skin, vasodilation and, at higher doses, the development of inflammation . As early as the 19th century, the Hungarian doctor Andreas Högyes (1847–1906) suspected an irritant effect on sensitive nerves. Around the middle of the 20th century, the group of the Hungarian pharmacologist Nicolas Jansó (1903–1966) in Szeged found that the irritation of sensitive nerves by capsaicin was followed by insensitivity to capsaicin itself and various other irritants such as isothiocyanates and formic acid and that in this state There were also no reactions to antidromic electrical stimulation of sensory nerves: Neither after capsaicin desensitization did antidromic vasodilation nor the accompanying "neurogenic plasma extravasation" described by Jancsó et al., collectively referred to as "neurogenic inflammation". In 1948 Hellauer and Umrath asked about the “action substance” for antidromic vasodilation. The Hungarian authors asked in 1967 about the "mediator substance" which mediated the neurogenic inflammation on the one hand when irritated by capsaicin and on the other hand when there was antidromic electrical stimulation of sensitive fibers and which was not released after capsaicin desensitization.

For Lembeck, a specification of the question was obvious. Was the "mediator substance" substance P? Three papers submitted for publication between March and September 1979 gave an affirmative answer. The vasodilation and plasma extravasation induced by antidromic electrical stimulation and those induced by substance P were very similar; for example, both were reduced by about half with antihistamines . Desensitizing pretreatment with capsaicin led to the disappearance of substance P from the tissue and a weakening of the neurogenic plasma extravasation. Finally, capsaicin released substance P from the spinal cord of rats from the dorsal horn , where the primarily afferent Aδ and C fibers end.

Tachykinin and capsaicin research remained intertwined. Capsaicin-sensitive substance P nerve fibers innervate not only the skin, but also internal organs such as the blood vessels, the trachea and the urinary and genital apparatus . In the urinary bladder, these fibers are stimulated when it is filled and mediate the micturition reflex ; after capsaicin desensitization there is no reflex. In the vagina and cervix uteri they are stimulated during copulation and mediate hormonal reactions; with capsaicin desensitization is nidation of the fertilized egg disturbed. Afferent capsaicin-sensitive neurons are also involved in regulating the release of adrenocorticotropin and prolactin from the pituitary gland .

Tachykinins in the intestinal nervous system. Primary afferent neuron green, neurons to the intestinal muscles black, sensitive neurons of the intestinal wall blue.

However, the number of capsaicin-sensitive neurons is not identical to the number of substance P-neurons. There are capsaicin-sensitive neurons with other transmitters, for example calcitonin gene-related peptides (CGRP), and vice versa, substance P neurons that are capsaicin-insensitive. The intestinal nervous system contains both primary afferent substance P nerve fibers that lead to the central nervous system, which are capsaicin-sensitive, as well as “intrinsic” nerve cells restricted to the intestinal wall, in which substance P is a cotransmitter with acetylcholine and which are capsaicin-insensitive. That is why the content of substance P in the intestine hardly decreases after treatment with capsaicin. During digestion, substance P is released in the intestinal wall. There it acts both directly on the smooth muscles and on neighboring nerve cells. In the years from 1980 onwards, Lembeck's Graz group helped to establish the knowledge of tachykinins in the intestinal nervous system - as his students Peter Holzer and Ulrike Holzer-Petsche presented them in reviews.

Antidromic vasodilation and neurogenic inflammation are clinically important beyond physiology and pharmacology, for example in bronchial asthma and migraines . In view of the transmitter function of substance P in pain fibers, it was expected that neurokinin receptor antagonists would be new analgesics . They are in animal experiments, but have so far been disappointing in humans. Instead, surprisingly, they have an antidepressant effect on humans . Lembeck himself presented the scientific and human aspects of tachykinin-capsaicin research in 2008 in an essay “The archeology of substance P”, which is typical of his sometimes columnar style - with original curves from his kymograph (intestinal contractions recorded on a sooty drum) and a copy of the note in the Frankfurter Allgemeine Zeitung.

The second substance in carcinoids

Lembeck had the satisfaction of confirming a possibility that he considered during his investigation of the carcinoid in 1953, but for which he had not found any evidence at the time: that the "second substance active in the intestine" (see above) was substance P. Other researchers found substance P in carcinoids using immunological methods in the 1970s. Lembeck, the pathologist Ratzenhofer and their colleagues secured this biochemically and pharmacologically in 1981. Enterochromaffin cells of the intestine that have not degenerated into tumor cells also contain serotonin and substance P.

Knowledge transfer and professional policy

His varied interest and knowledge allowed Lembeck to comment on general medical topics in quick succession, of course on the clinic of carcinoids, then on the "pharmacological-toxicological basis of drug side effects", "intolerances in mixed syringes", "basic features of practical digitalis therapy "," Childhood poisoning "," Savings in health insurance "," Alternatives to animal experiments "," Recording and assessing balneological healing effects "," Keeping laboratory animals "," Pharmacological effects on sleep "," Traveler's diarrhea "," Self-medication ", On the" toxicity of lipsticks ", on the" medicine in the doctor's bag ", on the" life of the rich man with his medicines ", on the package insert for finished medicinal products, on" bio-awareness ", on university and study problems.

Articles called, for example, “The clinician turns to rats”, “Animals teach students (animal experiments in the lecture and internship)”, “The bungling is increasing”, “Encouraging or thought-provoking - the German-language medical literature”, “Are natural substances better medicines? "," Teaching in Pharmacology "," Lollipops not even for dogs "," What is age and what is aging? "," Columbus, capsicum and capsaicin "," Pain and stress in the biological defense network "," From research to healing "," Successful errors and other odd ways to new discoveries ".

1964 appeared for the first time "The 1x1 des prescription", with own drawings and the explanation of the " prescription ": "It enables the drug to find its way to the patient. Long after the drug has fulfilled its function there and has taken the path of everything metabolic, a prescription is still in the paper mausoleum of a health insurance archive. ”Five further German and two Greek editions followed.

In 1965 a “Pharmacological Internship” was published, and in 1966 a “Pharmacology Primer” was published, which was published in another German, English and Japanese edition. In addition to the homage in the book with Josef Donnerer, Otto Loewi dedicated a detailed documentation to Lembeck . He also helped to create a film entitled “Nobel Prize Winner Otto Loewi”.

From 1967 to 1968 he was Dean of the Medical Faculty of the University of Tübingen, 1969 Chairman of the German Pharmacological Society and from 1972 to 1975 Secretary General of the International Union of Pharmacology (IUPHAR). From 1966 to 1983 he edited the Naunyn-Schmiedeberg Archive for Experimental Pathology and Pharmacology , which at the time was renamed Naunyn-Schmiedeberg's Archives of Pharmacology and was in English.

student

The following scientists completed their habilitation with Fred Lembeck in Tübingen or Graz (year of habilitation):

  • Dietrich Winne (1966), later head of a department for molecular pharmacology;
  • Karl Friedrich Sewing (1968), later professor in Hanover;
  • Heinrich Ochsenfahrt (1974), later Scientific Director of the Drugs Commission of the German Medical Association ;
  • Eckard Beubler (1980), who became professor at the Graz Institute in 1997 and headed it after Bernhard Peskar's retirement in 2007.
  • Hans Kopera (1980), who later headed clinical research at Organon ;
  • Rainer Gamse (1983), who later headed a research group at Novartis ;
  • Alois Saria (1984), who later headed the neurochemical department of the Psychiatric Clinic at the University of Innsbruck;
  • Peter Holzer (1985), since 2008 holder of a newly created professorship for experimental neurogastroenterology;
  • Josef Donnerer (1989), who headed the institute in the interval between Lembeck and Peskar;
  • Ulrike Holzer-Petsche (1993), later professor at the Graz Institute;
  • Rainer Amann (1991), later member of the Independent Medicines Commission in the Austrian Federal Ministry for Social Security and Generations ;
  • Thomas Griesbacher (1994), Amann's successor in the Independent Medicines Commission.

recognition

Lembeck was an honorary member of the Hungarian Pharmacological Society (1979), the German Society for Experimental and Clinical Pharmacology and Toxicology (1988), the Scientific Society of Doctors in Styria (1992) and the Austrian Pharmacological Society (2001) as well as a corresponding member of the Portuguese Pharmacological Society (1981).

He was a member of the German Academy of Sciences Leopoldina (1983), a corresponding member of the Austrian Academy of Sciences (1988) and a founding member of the Academia Europaea (1988).

In 1994 he received the Great Gold Medal of Honor of the State of Styria and in 1995 the Schmiedeberg plaque , the highest scientific award from the German Society for Experimental and Clinical Pharmacology and Toxicology.

In 1985 he received the Oscar Gans Award in Zurich and in 1987 the Louis and Arthur Lucian Award in Montreal .

literature

  • Josef Donnerer and Fred Lembeck: The Chemical Languages ​​of the Nervous System. Karger, Basel etc. 2006. ISBN 3-8055-8004-5 .
  • Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 358, 1998, pp. 1-109. doi : 10.1007 / PL00005229 .

Individual evidence

  1. ↑ a b Personal communication from his pupil Peter Holzer to user: Coranton .
  2. ↑ Donnerer and Lembeck 2006, p. 70.
  3. ↑ Zénon M. Bacq: Chemical transmission of nerve pulse. In: MJ Parnham and J. Bruinvels: Discoveries in Pharmacology, Volume 1. Elsevier, Amsterdam, etc. 1983, pp. 49-103. ISBN 0-444-80493-5 .
  4. ↑ Ernest H. Starling: The chemical coordination of body activities. Negotiations of the Society of German Natural Scientists and Doctors, 78th Assembly in Stuttgart, 16. – 22. September 1906. FCW Vogel, Leipzig 1907, pp. 246-260.
  5. ^ JH Gaddum and F. Lembeck: The assay of substances from the adrenal medulla . In: British Journal of Pharmacology and Chemotherapy . 4, 1949, pp. 401-408. PMC 1509922 (free full text).
  6. ^ F. Lembeck: Adrenalin, Noradrenalin and Corbasil as an additive to Novocain . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 217, 1953, pp. 274-279. doi : 10.1007 / BF00245469 .
  7. ^ F. Lembeck: 5-Hydroxytryptamine in a carcinoid tumor . In: Nature . 172, 1953, pp. 910-911. doi : 10.1038 / 172910a0 .
  8. ↑ F. Lembeck: About the detection of 5-oxytryptamine (enteramine, serotonin) in carcinoid metastases . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 221, 1954, pp. 50-66. doi : 10.1007 / BF00246931 .
  9. ^ F. Lembeck and K. Neuhold: Detection of 5-oxytryptamine in urine . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 226, 1955, pp. 456-459. doi : 10.1007 / BF00246284 .
  10. ↑ F. Lembeck, K.-Fr. Sewing and D. Winne: The influence of 5-hydroxyxtryptamine on the absorption of tritium water (HTO) from the small intestine of the rat . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 247, 1964, pp. 100-109. doi : 10.1007 / BF00245413 .
  11. ↑ H. Ochsenfahrt, D. Winne, K.-Fr. Sewing and F. Lembeck: The excretion of tritium water in the jejunum of the rat under the influence of 5-hydroxytryptamine and noradrenaline . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 254, 1966, pp. 261-269. doi : 10.1007 / BF00539921 .
  12. ↑ M. Berner Hansen and AB Witte: The role of serotonin in intestinal luminal sensing and secretion . In: Acta Physiologica . 193, 2008, pp. 311-323. doi : 10.1111 / j.1748-1716.2008.01870.x .
  13. ↑ E. Beubler and A. Schirgi-Degen: Serotonin antagonists inhibit sennoside-induced fluid secretion and diarrhea . In: Pharmacology . 47, Supplement 1, 1993, pp. 64-69. doi : 10.1159 / 000139844 .
  14. ^ A b F. Lembeck: On the question of the central transmission of afferent impulses. III. Message. The occurrence and importance of substance P in the dorsal roots of the spinal cord. . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 219, 1953, pp. 197-213. doi : 10.1007 / BF00246293 .
  15. ↑ Donnerer and Lembeck 2006, pp. 177-189.
  16. ↑ Starke 1998, pp. 60–61 and p. 91.
  17. ↑ W. Marktl: Univ.-Prof. Dr. Horst Hellauer 1913-2002 . In: Physical medicine, rehabilitation medicine, spa medicine . 12, 2002, pp. 296-297. doi : 10.1055 / s-2002-35156 .
  18. ↑ a b O. Loewi and H. Hellauer: About acetylcholine in peripheral nerves . In: Pflüger's archive for the entire physiology of humans and animals . 240, 1938, pp. 669-675. doi : 10.1007 / BF01759980 .
  19. ^ Otto Loewi: An autobiographic sketch. In: Fred Lembeck and Wolfgang Giere: Otto Loewi. A picture of life in documents. Springer-Verlag, Berlin, Heidelberg, New York 1968, pp. 168–190.
  20. ↑ O. Härtel and H. Heran: To commemorate. Karl Umrath (March 26, 1899 - November 26, 1985) . (pdf file; 1.4 MB)
  21. ↑ HF Hellauer and Karl Umrath: About the action substance of the sensory nerves . In: Pflüger's archive . 249, 1948, pp. 619-630. doi : 10.1007 / BF00362864 .
  22. ↑ K. Umrath and HF Hellauer: The occurrence of the sensitive substance and of action substances degrading ferments . In: Pflüger's archive . 250, 1948, pp. 737-746. doi : 10.1007 / BF00362883 .
  23. ↑ US v. Euler and JH Gaddum: An unidentified depressor substance in certain tissue extracts . In: The Journal of Physiology . 72, 1931, pp. 74-87. PMC 1403098 (free full text).
  24. ↑ Bengt Pernow: Substance P . In: Pharmacological Reviews . 35, 1983, pp. 85-141, here p. 126. PMID 6196797 .
  25. ↑ T. Hökfelt, B. Pernow and J. Wahren: Substance P: a pioneer amongst neuropeptides . In: Journal of Internal Medicine . 249, 2001, pp. 27-40. doi : 10.1046 / j.0954-6820.2000.00773.x .
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  31. ↑ F. Lembeck and K. Starke: Substance P content and effect on capillary permeability of extracts of various parts of human brain . In: Nature . 199, 1963, pp. 1295-1296. doi : 10.1038 / 1991295a0 .
  32. ↑ A. Heizmann and F. Lembeck: Substantia P content and capillary permeability in extracts from substantia nigra . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 253, 1966, pp. 260-264. doi : 10.1007 / BF00246376 .
  33. ^ Vittorio Erspamer: Biogenic amines and active polypeptides of the amphibian skin . In: Annual Review of Pharmacology . 11, 1971, pp. 327-350. doi : 10.1146 / annurev.pa.11.040171.001551 .
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  35. ↑ a b F. Lembeck and K. Starke: Substance P and saliva secretion . In: Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology . 259, 1968, pp. 375-385. doi : 10.1007 / BF00538551 .
  36. ↑ F. Lembeck, A. Oberdorf, K. R. and Strong Hettich: Sialogene and smooth muscle effects of physalaemin derivatives and substance P . In: Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology . 261, 1968, pp. 338-345. doi : 10.1007 / BF00537178 .
  37. ↑ F. Lembeck, F. Geipert and K. Starke: Simultaneous effect of peptides in chickens . In: Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology . 261, 1968, pp. 422-433. doi : 10.1007 / BF00537559 .
  38. ↑ Donnerer and Lembeck 2006, p. 179.
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  41. ↑ Michael M. Chang, Susan E. Leeman and Hugh D. Niall: amino acid sequence of substance P . In: Nature New Biology . 232, 1971, pp. 86-87. Text at Nature . Retrieved April 10, 2012.
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  43. ↑ Fred Lembeck, Josef Donnerer and Loránd Barthó: Inhibition of neurogenic vasodilation and plasma extravasation by substance P antagonists, somatostatin and [D-Met 2 , Pro 5 ] enkephalinamide . In: European Journal of Pharmacology . 85, 1982, pp. 171-176. doi : 10.1016 / 0014-2999 (82) 90462-9 .
  44. ↑ Fred Lembeck, Josef Donnerer, Megumi Tsuchiya and Atsushi Nagahisa: The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of neurogenic inflammation . In: British Journal of Pharmacology . 105, 1992, pp. 527-530. PMC 1908444 (free full text).
  45. ↑ FJ Legat, T. Griesbacher and F. Lembeck: CP-96,345, a non-peptide antagonist of substance P: I. Effects on the actions mediated by substance P and related tachykinins on the guinea-pig ileum and rabbit jejunum . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 346, 1992, pp. 315-322. doi : 10.1007 / BF00173545 .
  46. ↑ T. Griesbacher, J. Donnerer, FJ Legat and F. Lembeck: CP-96,345, a non-peptide antagonist of substance P: II. Actions on substance P-induced hypotension and bronchoconstriction, and on depressor reflexes in mammals . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 346, 1992, pp. 323-327. doi : 10.1007 / BF00173546 .
  47. ↑ J. Donnerer, U. Stark, HA Tritthart and F. Lembeck: CP-96,345, a non-peptide antagonist of substance P. III. Cardiovascular effects unrelated to actions on substance P receptors . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 346, 1992, pp. 328-332. doi : 10.1007 / BF00173547 .
  48. ^ Andreas Högyes: Contributions to the physiological effect of the constituents of Capsicum annuum (Spanish pepper) . In: Archives of Experimental Pathology and Pharmacology . 9, 1878, pp. 117-130. doi : 10.1007 / BF02125956 .
  49. ↑ Starke 1998, p. 25.
  50. ↑ Starke 1998, p. 68.
  51. ↑ N. Jancsó, Aurelia Jancsó-Gabor and J. Szolcsányi: Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin . In: British Journal of Pharmacology and Chemotherapy . 31, 1967, pp. 138-151. PMC 1557289 (free full text).
  52. ↑ Fred Lembeck and Peter Holzer: Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 310, 1979, pp. 175-183. doi : 10.1007 / BF00500282 .
  53. ↑ R. Gamse, P. Holzer and F. Lembeck: Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaicin . In: British Journal of Pharmacology . 68, 1980, pp. 207-213. PMC 2043922 (free full text).
  54. ↑ Rainer Gamse, Ann Molnar and Fred Lembeck: Substance P release from spinal cord slices by capsaicin . In: Life Sciences . 25, 1979, pp. 629-636. doi : 10.1016 / 0024-3205 (79) 90558-7 .
  55. ↑ Ann Bucsics and Fred Lembeck: In vitro release of substance P from spinal cord slices by capsaicin congeners . In: European Journal of Pharmacology . 71, 1981, pp. 71-77. doi : 10.1016 / 0014-2999 (81) 90387-3 .
  56. ↑ P. Holzer, A. Bucsics and F. Lembeck: Distribution of capsaicin-sensitive nerve fibers containing immunoreactive substance P in cutaneous and visceral tissues of the rat . In: Neuroscience Letters . 31, 1982, pp. 253-257. doi : 10.1016 / 0304-3940 (82) 90029-5 .
  57. ↑ Harold Traurig, Alois Saria and Fred Lembeck: Substance P in primary afferent neurons of the female rat reproductive system . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 326, 1984, pp. 343-346. doi : 10.1007 / BF00501440 .
  58. ↑ a b Harold Traurig, Alois Saria and Fred Lembeck: The effects of neonatal capsaicin treatment on growth and subsequent reproductive function in the rat . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 327, 1984, pp. 254-259. doi : 10.1007 / BF00502458 .
  59. ^ U. Holzer-Petsche, F. Lembeck: Systemic capsaicin treatment impairs the micturition reflex in the rat. In: British journal of pharmacology. Volume 83, Number 4, December 1984, pp. 935-941, PMID 6518344 , PMC 1986977 (free full text).
  60. ↑ Josef Donnerer and Fred Lembeck: Neonatal capsaicin treatment of rats reduces ACTH secretion in response to peripheral neuronal stimuli but not to centrally acting stressors . In: British Journal of Pharmacology . 94, 1988, pp. 647-652. PMC 1854037 (free full text).
  61. ↑ Josef Donnerer and F. Lembeck: Different control of the adrenocorticotropin-corticosterone response and of prolactin secretion during cold stress, anesthesia, surgery, and nicotine injection in the rat: involvement of capsaicin-sensitive sensory neurons . In: Endocrinology . 126, 1990, pp. 921-926. doi : 10.1210 / endo-126-2-921 .
  62. ↑ Peter Holzer, Rainer Gamse and Fred Lembeck: Distribution of substance P in the rat gastrointestinal tract - lack of effect of capsaicin pretreatment . In: European Journal of Pharmacology . 61, 1980, pp. 303-307. doi : 10.1016 / 0014-2999 (80) 90132-6 .
  63. ↑ J. Thunderer L. Bartho, P. Holzer and F. Lembeck: intestinal peristalsis associated with release of immunoreactive substance P . In: Neuroscience . 11, 1984, pp. 913-918. doi : 10.1016 / 0306-4522 (84) 90202-1 .
  64. ↑ Josef Donnerer, Peter Holzer and Fred Lembeck: Release of dynorphin, somatostatin and substance P from the vascularly perfused small intestine of the guinea-pig during peristalsis . In: British Journal of Pharmacology . 83, 1984, pp. 919-925. PMC 1986988 (free full text).
  65. ↑ P. Holzer and F. Lembeck: Neurally mediated contraction of ileal longitudinal muscle by substance P . In: Neuroscience Letters . 17, 1980, pp. 101-105. doi : 10.1016 / 0304-3940 (80) 90069-5 .
  66. ↑ L. Barthó, P. Holzer, S. Leander and F. Lembeck: Evidence for an involvement of substance P, but not cholecystokinin-like peptides, in hexamethonium-resistant intestinal peristalsis . In: Neuroscience . 28, 1989, pp. 211-217. doi : 10.1016 / 0306-4522 (89) 90245-5 .
  67. ↑ Peter Holzer and Ulrike Holzer-Petsche: Tachykinins in the gut. Part I. Expression, release and motor function . In: Pharmacology & Therapeutics . 73, 1997, pp. 173-217. doi : 10.1016 / S0163-7258 (96) 00195-7 .
  68. ↑ P. Holzer: Role of tachykinins in the gastrointestinal tract. In: Peter Holzer (ed.): Tachykinins , pp. 511–558. Springer-Verlag, Berlin etc. 2004. ISBN 3-540-20690-6 .
  69. ↑ Klaus Starke: Pharmacology of noradrenergic and adrenergic systems - Pharmacotherapy of bronchial asthma - Doping. In: K. Aktories, U. Förstermann, F. Hofmann and K. Starke: General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pages 161-199. ISBN 978-3-437-42522-6 .
  70. ↑ M. Göthert and H.-Ch. Diener: pharmacology of serotonin - pharmacotherapy of primary headache. In: K. Aktories, U. Förstermann, F. Hofmann and K. Starke: General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pages 201-209. ISBN 978-3-437-42522-6 .
  71. ↑ Pierangelo Geppetti, Eleonora Rossi, Alberto Chiarugi and Silvia Benemei: Antidromic vasodilatation and the migraine mechanism . In: Journal of Headache and Pain . 13, 2012, pp. 103-111. doi : 10.1007 / s10194-011-0408-3 .
  72. ^ S. Boyce and RG Hill: Substance P (NK 1 ) receptor antagonists - analgesics or not? In: Peter Holzer (ed.): Tachykinins , pp. 441–457. Springer-Verlag, Berlin etc. 2004. ISBN 3-540-20690-6 .
  73. ↑ NMJ Rupniak: Therapeutic potential of tachykinin receptor antagonists in depression and anxiety disorders. In: Peter Holzer (ed.): Tachykinins , pp. 341–357. Springer-Verlag, Berlin etc. 2004. ISBN 3-540-20690-6 .
  74. ↑ Fred Lembeck: The archeology of substance P . In: Neuropeptides . 42, 2008, pp. 444-453. doi : 10.1016 / j.npep.2008.04.006 .
  75. ↑ M. Ratzenhofer, R. Gamse, H. Höfler, L. Auböck, H. Popper, P. Pohl and F. Lembeck: Substance P in an argentaffin carcinoid of the caecum: biochemical and biological characterization . In: Virchow Archives A . 392, 1981, pp. 21-31. doi : 10.1007 / BF00430545 .
  76. ^ Fred Lembeck: Successful errors and other odd ways to new discoveries . In: Medical History . 11, 1967, pp. 157-164. PMC 1033696 (free full text).
  77. ↑ Fred Lembeck: The 1x1 of recipe. Georg Thieme-Verlag, Stuttgart 1964.
  78. ↑ Fred Lembeck and Dietrich Winne: Pharmacological internship. Georg Thieme-Verlag, Stuttgart 1965.
  79. ↑ Fred Lembeck and Karl-Friedrich Sewing: Pharmakologie-Fibel. Boards for the pharmacology lecture. Springer-Verlag, Berlin etc. 1966.
  80. ↑ Fred Lembeck and Wolfgang Giere: Otto Loewi. A picture of life in documents. Springer-Verlag, Berlin, Heidelberg, New York 1968
  81. ↑ Donnerer and Lembeck 2006, p. 82.
  82. ^ Jürgen Lindner and Heinz Lüllmann: Pharmacological institutes and biographies of their directors. Aulendorf, Editio-Cantor-Verlag 1996. ISBN 3-87193-172-1 .
  83. ^ Athineos Philippu: History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Volume III. Complement. Berenkamp-Verlag, Wattens 2011. ISBN 978-3-85093-281-3 .
  84. ^ Karl Friedrich Sewing: Obituary for Fred Lembeck (1922-2014). In: Biospektrum 21, 2015, p. 103. Digitized. Retrieved February 20, 2015.

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personal data
SURNAME Lembeck, Fred
BRIEF DESCRIPTION Austrian doctor and pharmacologist
DATE OF BIRTH 4th July 1922
PLACE OF BIRTH Herzogenburg-Ober Winden
DATE OF DEATH October 22, 2014
Place of death Graz