Athineos Philippu

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Athineos Philippu

Athineos Philippu (Αθήναιος Φιλίππου; alternative transliteration Athineos Philippou; born September 22, 1931 in Athens ) is a Greek - German - Austrian doctor and pharmacologist .

Life

His parents were the lawyer Ioannis Philippou and his wife Andromachi. Athineos attended schools in Athens and studied medicine there from 1950 to 1956. In addition to his studies, he mainly worked on the cholinesterase activity of various types of leukocytes and the chromatographic separation of carbohydrates as a student assistant and doctoral candidate at the Physiological Institute of the University of Athens with Christos Maltesos, a student of Hermann Rein . In 1959 he was awarded a PhD with a dissertation entitled "On the cholinesterase activity of various leukocytes" (from the Greek). med. PhD . He then did two and a half years of military service in the Greek Navy. From 1959 to 1962 he worked as a fellow of the Alexander von Humboldt Foundation, first at the Physiological Institute of the University of Cologne , and from 1960 onwards at the Pharmacological Institute of the Johann Wolfgang Goethe University in Frankfurt am Main , headed by Peter Holtz . There he then became a research assistant. In 1965 he completed his habilitation with a thesis "Investigations into the mechanism of storage and release of the adrenal medulla hormones" for pharmacology and toxicology . When his Frankfurt mentor, the older Holtz student Hans-Joachim Schümann , became director of the newly founded Pharmacological Institute of the Essen University Clinic in what is now the University of Duisburg-Essen in 1964 , Philippu followed him. In 1968 he spent two months researching with Wilhelm Feldberg at the National Institute for Medical Research in London. From 1970 to 1982 he was professor and head of department at Ullrich Georg Trendelenburg at the Institute for Pharmacology and Toxicology at the Julius Maximilians University of Würzburg . In 1982 he was appointed professor and founding board member at the Institute for Pharmacodynamics and Toxicology , later renamed "Institute for Pharmacology and Toxicology since", 1999 Department for Pharmacology and Toxicology of the Institute for Pharmacy of the Faculty of Chemistry and Pharmacy at the University of Innsbruck . Retired in 1999, he continues to live in Innsbruck . His successor was Jörg Striessnig (* 1959).

research

At the Physiological Institute of the University of Athens he worked as a student on the cholinesterase activity of various types of leukocytes, the results he published as the sole author in the American Journal of Physiology , Blood , Nature . In the group of Holtz and Schümann in Frankfurt am Main , Philippu discovered the pharmacology of the nervous system. It was about the storage granules (vesicles) (also storage vesicles ), which store the catecholamines (pyrocatecholamines) noradrenaline and adrenaline in the cells of the adrenal medulla and in nerve cells . It was known that indirect sympathomimetics like tyramine released the catecholamines. Schümann and Philippu examined this more closely using isolated vesicles from the adrenal medulla. Tyramine released the catecholamines, but not the adenosine triphosphate stored with them , and at the same time it was taken up into the vesicles itself. Other indirect sympathomimetics such as ephedrine and amphetamine had a similar effect : Schümann and Philippu concluded: “The evidence we have provided that the amounts of catecholamine released from the isolated adrenal medulla granules under the action of tyramine are replaced by an intake of tyramine in a stoichiometric ratio suggests that it is is a mechanism of repression. ”The descriptive word“ repression ”is a simplified description of the mechanism of action of the much misused and medicinally used indirect sympathomimetics. The Frankfurt group has shown that the release of catecholamines from chromaffin vesicles can be induced by tyramine, β- phenethylamine , amphetamine, methamphetamine and ephedrine, but not by adenosine triphosphate. Furthermore, the working group was able to show that tyramine and β-phenethylamine accumulate in chromaffin vesicles, in a stoichiometric ratio with the catecholamine release. They concluded that amphetamine and similar compounds act by displacing the catecholamines with no equivalent release of ATP.

The vesicles have to take up their catecholamines from the cytoplasm . Philip's group showed, along with other researchers, that uptake is an active transport in which adenosine triphosphate is cleaved in adrenal medulla vesicles as well as in the vesicles of postganglionic sympathetic nerves and the vesicles of norepinephrine neurons of the brain. Other neurotransmitters such as dopamine and γ-aminobutyric acid also reach their storage vesicles through adenosine triphosphate-dependent transport.

With the move from Essen to Würzburg, research on the nervous system of living test animals increasingly replaced research on cell organelles ; neurochemical measurements continued to prevail. In Essen, Philippu measured the release of noradrenaline in the hypothalamus of anesthetized cats for the first time . Two years later, he used push-pull cannulas inserted into the brain for the first time. They consist of two concentric tubes. Liquid is pressed through the inner tube into the small brain area to be examined; it flows out again through the outer tube (more precisely the space between the inner and outer tube). Substances that diffuse from the brain into the fluid, such as neurotransmitters, can be measured in this “superfusate”. In addition, the brain area can be electrically stimulated by the tip of the inner cannula, which is not electrically isolated. Philippu has improved the cannulas over time so that they could also be used, for example, with small test animals such as rats and with conscious, freely moving animals.

With this method, Philippu mainly examined the importance of different brain areas and different neurotransmitters for the regulation of arterial blood pressure . Electrical stimulation of the posterior hypothalamus increased blood pressure, and electrical stimulation of the anterior hypothalamus decreased it. If the arterial pressure was experimentally increased (for example by means of vasoconstricting substances ) or decreased (for example by means of vasodilating substances ), the release of neurotransmitters in the hypothalamus changed, often in opposite directions in the posterior and anterior hypothalamus: In the posterior hypothalamus was the release of noradrenaline, adrenaline and dopamine is reduced when the blood pressure is increased (by means of vasoconstricting substances) and increased by a decrease in blood pressure (by means of vasodilating substances); In the anterior hypothalamus, on the other hand, the release of the three transmitters was increased when the blood pressure was increased (by means of vasoconstricting substances) and decreased when the blood pressure was lowered (by means of vasodilating substances). Analogous measurements in other brain areas such as the nucleus tractus solitarii and the locus caeruleus as well as for other transmitters such as histamine and serotonin followed. The release of norepinephrine in the locus caeruleus responded to changes in blood pressure such as the release in the posterior hypothalamus, for example, decreased when the blood pressure was increased by a vasoconstrictor substance. Severing the nerves leading from the baroreceptors to the brain prevented reactions in the locus caeruleus and the posterior hypothalamus, perhaps because the severing removed inhibition by γ-aminobutyric acid. The group thus approached an overall picture of central nervous blood pressure regulation.

The neuropharmacology of histamine became another research focus. The neurotransmitters histamine and acetylcholine mutually influenced their release. In the posterior hypothalamus, the release of histamine was subject to an ultradian rhythm that correlated with ultradian fluctuations in the electroencephalogram . Histamine promoted short-term memory in rats. "Histamine and acetylcholine neurons and their interaction seem to play an important role in thought processes ('cognition')."

One of the best-known publications, Philippus, is only 1½ page long, in which he and his colleague Helmut Prast described a new possible effect of nitric oxide (NO) in 1992 : an inhibitor of the NO-forming enzyme NO synthase reduced the release of acetylcholine in the forebrain of rats in vivo , while linsidomine , from which NO is formed, increased the release. Similar findings were made elsewhere in vitro in the same year. The Innsbruck group itself extended its investigation to the release of histamine and glutamic acid in the hypothalamus and the release of serotonin in the locus caeruleus. In 1992, NO was identified as a biological signaling molecule only five years ago, and that explains the interest. Prast and Philippu summarized the neurobiology of nitric oxide in 2001 in a review article. "NO, released from nerve cells, appears to be a general modulator of neurotransmitter release."

Editorial activity

From 1972 to 1999, Philippu was Editor or Advisory Editor of Naunyn-Schmiedeberg's Archives of Pharmacology . In 2004 he published the 1032-page work "History and Work of the Pharmacological, Clinical-Pharmacological and Toxicological Institutes in German-speaking Countries". A second volume, mainly Pictures, followed in 2007, a third, supplementary volume in 2011, and a final volume IV, Autobiographies in 2014.

recognition

The University of Helsinki awarded Philippu in 1977 and the University of Innsbruck in 1999 its university medal. In 2008 he received an honorary doctorate from the Medical Faculty of the Aristotle University of Thessaloniki .

Individual evidence

  1. ↑ Athineos Philippu: Department of Pharmacology and Toxicology, Institute of Pharmacy, Natural Science Faculty of the Leopold-Franzens University Innsbruck. In: Athineos Philippu (Ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004, pp. 371–377. ISBN 3-85093-180-3 .
  2. ↑ AJ Philippu: Cholinesterase of leucocytes. In: The American journal of physiology. Volume 184, Number 1, January 1956, pp. 145-146, ISSN  0002-9513 . PMID 13283105 .
  3. ^ AJ Philippu: A method for the separation of the different morphologic forms of the blood leukocytes. In: Blood. Volume 11, Number 11, November 1956, pp. 1041-1044, ISSN  0006-4971 . PMID 13364014 .
  4. ↑ AJ Philippu: Cholinesterase Content of the Dog's Lymphocytes and Polynuclears. In: Nature. 180, 1957, pp. 438-438, doi : 10.1038 / 180438a0 .
  5. ^ AJ Philippu: A Simple, Rapid Method for Circular Paper Chromatography. In: Nature. 182, 1958, pp. 1159-1159, doi : 10.1038 / 1821159a0 .
  6. ↑ Philippu A. (1959): Quantitative determination of reducing sugars after separation by paper chromatography. Anal. Chemistry 31: 1615.
  7. ↑ Philippu A. (1959): Separation of galactose, glucose and lactose in urine by paper chromatography. Anal. Chemistry 31: 1743-1744.
  8. ↑ AJ Philippu: A paper chromatographic method for lactase and maltase activity determination. In: Enzymologia. Volume 21, January 1960, pp. 216-218, ISSN  0013-9424 . PMID 14432594 .
  9. ↑ HJ Schümann and A. Philippu: Investigations on the mechanism of the release of catecholamines by tyramine . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 241, 1961, pp. 273-280. doi : 10.1007 / BF00246593 .
  10. ^ HJ Schümann and A. Philippu: Release of catechol amines from isolated medullary granules by sympathomimetic amines . In: Nature . 193, 1962, pp. 890-891. doi : 10.1038 / 193890a0 .
  11. ↑ Klaus Starke: Pharmacology of noradrenergic and adrenergic systems. In: K. Aktories, U. Förstermann, F. Hofmann and K. Starke: General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pp. 161-199. ISBN 978-3-437-42522-6
  12. ↑ HJ Schümann and A. Philippu: Investigations on the mechanism of the release of catecholamines by tyramine . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 241, 1961, pp. 273-280. doi : 10.1007 / BF00246593 .
  13. ^ Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 2358, 1998, pp. 1–109, here p. 64. doi : 10.1007 / PL00005229 .
  14. ↑ N. Singewald, D. Kouvelas, F. Chen, A. Philippu: The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations. In: Naunyn-Schmiedeberg's archives of pharmacology. Volume 356, Number 3, September 1997, pp. 348-355. PMID 9303572 .
  15. ^ A b c D. Sulzer, MS Sonders, NW Poulsen, A. Galli: Mechanisms of neurotransmitter release by amphetamines: a review. In: Progress in neurobiology. Volume 75, Number 6, April 2005, pp. 406-433. doi : 10.1016 / j.pneurobio.2005.04.003 . PMID 15955613 . PDF .
  16. ↑ A. Burger, A. Philippu and HJ Schümann: ATP cleavage and amine uptake by splenic nerve granules . In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 262, 1969, pp. 208-220. doi : 10.1007 / BF00537661 .
  17. ^ A. Philippu, U. Burkat and H. Becke: Uptake of norepinephrine by the isolated hypothalamic vesicles . In: Life Sciences . 7, 1968, pp. 1009-1017. doi : 10.1016 / 0024-3205 (68) 90207-5 .
  18. ^ A. Philippu and J. Beyer: Dopamine and noradrenaline transport into subcellular vesicles of the striatum . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 278, 1973, pp. 397-402. doi : 10.1007 / BF00501482 .
  19. ^ A. Philippu and M. Matthaei: Uptake of serotonin, gamma-aminobutyric acid and histamine into synaptic vesicles of the pig caudate nucleus . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 287, 1975, pp. 191-204. doi : 10.1007 / BF00510450 .
  20. ^ A. Philippu, G. Heyd and A. Burger: Release of noradrenaline from the hypothalamus in vivo . In: European Journal of Pharmacology . 9, 1970, pp. 52-58. doi : 10.1016 / 0014-2999 (70) 90320-1 .
  21. ↑ A. Philippu, H. and W. Przuntek Roensberg: superfusion of the hypothalamus with gamma-aminobutyric acid. Effect on release of noradrenaline and blood pressure . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 276, 1973, pp. 103-118. doi : 10.1007 / BF00501183 .
  22. ↑ Athineos Philippu: Use of push-pull cannulae to determine the release of endogenous neurotransmitters in distinct brain areas of anaesthetized and freely moving animals. In: CA Marsden (Ed.): Measurement of Neurotransmitter Release In Vivo , pp. 3-37. John Wiley & Sons Ltd., 1984.
  23. ^ Athineos Philippu, Hans Dietl and Albert Eisert: Hypotension alters the release of catecholamines in the hypothalamus of the conscious rabbit . In: European Journal of Pharmacology . 69, 1981, pp. 519-523. doi : 10.1016 / 0014-2999 (81) 90461-1 .
  24. ^ RL Robinson, H. Dietl, M. Bald, A. Kraus and A. Philippu: Effects of short-lasting and long-lasting blood pressure changes on the release of endogenous catecholamines in the hypothalamus of the conscious, freely moving rabbit . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 322, 1983, pp. 203-209. doi : 10.1007 / BF00500766 .
  25. ↑ A. Klausmair, N. Singewald and A. Philippu: release of endogenous catecholamines in two different regions of the nucleus of the solitary tract as Influenced by carotid occlusion . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 343, 1991, pp. 155-160. doi : 10.1007 / BF00168603 .
  26. ↑ a b N. Singewald and A. Philippu: catecholamines release in the locus coeruleus is modified by experimentally induced changes in haemodynamics . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 347, 1993, pp. 21-27. doi : 10.1007 / BF00168767 .
  27. ^ A. Philippu, R. Hagen, U. Hanesch and U. Waldmann: Changes in the arterial blood pressure increase the release of endogenous histamine in the hypothalamus of anaesthetized cats . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 323, 1983, pp. 162-167. doi : 10.1007 / BF00634265 .
  28. ↑ Nicolas Singewald, Lian jun Guo, Christoph Schneider, Stefan Kaehler and Athineos Philippu: Serotonin outflow in the hypothalamus of conscious rats: origin and possible involvement in cardiovasculat control . In: European Journal of Pharmacology . 294, 1995, pp. 787-793. doi : 10.1016 / 0014-2999 (95) 00652-4 .
  29. ↑ Christoph Schneider, Nicolas Singewald and Athineos Philippu: Inhibition of catecholamine (noradrenaline, dopamine) release in the locus coeruleus and the hypothalamus by baroreceptor activation: identification of the involved baroreceptors . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 352, 1995, pp. 291-296. doi : 10.1007 / BF00168559 .
  30. ↑ Dimitrios Kouvelas, Nicolas Singewald, Stefan T. Kaehler and Athineos Philippu: Sinoaortic denervation abolishes blood pressure-induced GABA release in the locus coeruleus of conscious rats . In: Neuroscience Letters . 393, 2006, pp. 194-199. doi : 10.1016 / j.neulet.2005.09.063 .
  31. ↑ Athineos Philippu: Regulation of blood pressure by central neurotransmitters and neuropeptides . In: Reviews of Physiology, Biochemistry and Pharmacology . 111, 1988, pp. 1-115. doi : 10.1007 / BFb0033872 .
  32. ↑ Nicolas Singewald and Athineos Philippu: Involvement of biogenic amines and amino acids in the central regulation of cardiovascular homeostasis . In: Trends in Pharmacological Sciences . 17, 1996, pp. 356-363. doi : 10.1016 / S0165-6147 (96) 10042-0 .
  33. ^ Athineos Philippu and Helmut Prast: Importance of histamine in modular processes, locomotion and memory . In: Behavioral Brain Research . 124, 2001, pp. 151-159. doi : 10.1016 / S0166-4328 (01) 00226-1 .
  34. ↑ H. Prast, HP Fischer, M. Prast and A. Philippu: In vivo modulation of histamine release by autoreceptors and muscarinic acetylcholine receptors in the rat anterior hypothalamus . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 350, 1994, pp. 599-604. doi : 10.1007 / BF00169363 .
  35. ↑ Helmut Prast, Manh Hung Tran, Claudia Lamberti, Hanspeter Fischer, Michaela Kraus, Kurt Grass and Athineos Philippu: Histaminergic neurons modulate acetylcholine release in the ventral striatum: role of H 1 and H 2 histamine receptors . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 360, 1999, pp. 552-557. doi : 10.1007 / s002109900098 .
  36. ^ Helmut Prast, Kurt Grass and Athineos Philippu: The ultradian EEG rhythm coincides temporally with the ultradian rhythm of histamine release in the posterior hypothalamus . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 356, 1997, pp. 526-528. doi : 10.1007 / PL00005086 .
  37. ↑ Helmut Prast, Anastasia Argyriou and Athineos Philippu: Histaminergic neurons facilitate social memory in rats . In: Brain Research . 734, 1996, pp. 316-318. doi : 10.1016 / 0006-8993 (96) 00886-4 .
  38. ↑ Athineos Philippu and Helmut Prast: Role of histaminergic and cholinergic transmission in cognitive processes . In: Drug News & Perspectives . 14, 2001, pp. 523-529. doi : 10.1358 / dnp.2001.14.9.858409 .
  39. ↑ Helmut Prast and Athineos Philippu: Nitric oxide releases acetylcholine in the basal forebrain . In: European Journal of Pharmacology . 216, 1992, pp. 139-140. doi : 10.1016 / 0014-2999 (92) 90223-Q .
  40. ↑ Helmut Prast, Claudia Lamberti, Hanspeter Fischer, Manh Hung Tran and Athineos Philippu: Nitric oxide influences the release of histamine and glutamate in the rat hypothalamus . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 354, 1996, pp. 731-735. doi : 10.1007 / BF00166899 .
  41. ↑ Stefan T. Kaehler, Nicolas Singewald, Catrin Sinner and Athineos Philippu: Nitric oxide modulates the release of serotonin in the rat hypothalamus . In: Brain Research . 835, 1999, pp. 346-349. doi : 10.1016 / S0006-8993 (99) 01599-1 .
  42. ↑ Helmut Prast and Athineos Philippu: Nitric oxide as modulator of neuronal function . In: Progress in Neurobiology . 64, 2001, pp. 51-68. doi : 10.1016 / S0301-0082 (00) 00044-7 .
  43. ↑ Athineos Philippu (ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Berenkamp-Verlag, Innsbruck 2004. ISBN 3-85093-180-3 .
  44. ↑ Athineos Philippu (ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Volume II. Illustrated book and supplement. Berenkamp-Verlag, Innsbruck 2007. ISBN 978-3-85093-214-1 .
  45. ↑ Athineos Philippu (ed.): History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Volume III. Complement. Berenkamp-Verlag, Innsbruck 2011. ISBN 978-3-85093-281-3 .
  46. ^ Athineos Philippu: History and work of the pharmacological, clinical-pharmacological and toxicological institutes in German-speaking countries. Volume IV Autobiographies. Berenkamp-Verlag, Innsbruck 2011. ISBN 978-3-85093-325-4 .
personal data
SURNAME Philippu, Athineos
ALTERNATIVE NAMES Φιλίππου, Αθήναιος; Philippou, Athineos
BRIEF DESCRIPTION German pharmacologist
DATE OF BIRTH September 22, 1931
PLACE OF BIRTH Athens