Serafim Guimarães

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Serafim Guimarães

Serafim Guimarães , full name Serafim Correia Pinto Guimarães , (born May 2, 1934 in Espargo , a village near the city of Santa Maria da Feira in the Portuguese Norte region ), is a Portuguese doctor and pharmacologist . Together with his colleague Walter Osswald (* 1928) he turned the Pharmacological Institute of the Medical Faculty of the University of Porto into a center for research on catecholamines and the sympathetic nervous system , especially with regard to the control of blood vessels .

Life

The father, drawn by Serafim Guimarães
Ullrich Trendelenburg, drawn by Serafim Guimarães

Serafim Guimarães is the second son of the farmer Américo Ferreira Pinto Guimarães and his wife Maria Emília Correia nee. Pais. Serafim attended schools in Espargo and Espinho . He then studied medicine at the University of Porto and also worked at the Pharmacological Institute. In 1960 he received his Licenciatura , the medical license to practice medicine . After military service in Angola from November 1963 to December 1965, he returned to the Pharmacological Institute. In 1966, on a grant from the Alexander von Humboldt Foundation, he spent five months at the Pharmacological Institute of the Essen University Hospital with Hans-Joachim Schümann , and in 1971 and 1977 nine months at the Pharmacological Institute of the Julius Maximilians University of Würzburg near Ullrich Trendelenburg . In his book “Retratos legendados” he set a monument in pictures and words for Trendelenburg, with whom he also published together. In 1968 he was in Porto with a dissertation Recep gate Adrenérgicos - Ensaio de Interpretação e Análise ( adrenoceptor - an attempt at interpretation and analysis ) for Ph.D. PhD . In 1973 he was appointed Associate Professor of Pharmacology and Therapy, dismissed in April 1974 in the course of the Carnation Revolution , reinstated in November 1975 after the crackdown on the pro-communist coup of November 25th and full professor in 1979. From 1990 to 2005 he headed the Pharmacological Institute. In 2005 he retired . His successor was Patrício Soares-da-Silva (* 1957), who had obtained his Ph.D. degree under the supervision of Walter Osswald. With his wife Maria de Fátima geb. Martins de Sousa, whom he married in Braga in 1964 , Serafim Guimarães has two sons and a daughter.

research

The state of research at the time of Guimarães' entry into the Pharmacological Institute is exemplified by a discovery from 1966 in which Walter Osswald, Alberto Malafaya-Baptisa (1903–1966) and José Ruiz de Almeida Garrett (1919–1996) were involved. They were able to reverse the adrenaline reversal - the reversal of the blood pressure-increasing effect of the catecholamine adrenaline into a blood pressure lowering after blockage of the α-adrenoceptors by phenoxybenzamine - in turn into an increase in blood pressure if they additionally blocked the β-adrenoceptors. The cautious explanation that there are phenoxybenzamine-insensitive α-adrenoceptors was confirmed a few years later by the distinction between two subgroups of α-adrenoceptors, α 1 (phenoxybenzamine-sensitive) and α 2 (phenoxybenzamine-insensitive): The discovery from Porto had pointed to the future.

One of Guimarães' first research also indicated two α-adrenoceptor subgroups. A second work from the same year (with Walter Osswald) was devoted to the pharmacology of veins , about which little was known compared to arteries . All effects of the catecholamines adrenaline, noradrenaline , dopamine and isoprenaline could be explained with an effect as agonists , activating substances, on coexisting α- and β-adrenoceptors in the smooth muscles . Veins and their receptors remained popular objects of research. With Walter Osswald, Guimarães summarized the knowledge about blood vessels, their nerves and their influence by catecholamines in 1983, with his student Daniel Moura in 2001 in review articles. The 1983 article carries as a motto, the verses from the Cherubini Wanderer of Angelus Silesius

The rose is without why
it blooms because it blooms

- “in which the great Silesian poet of ther seventeenth century reminds us that Nature may need no justification of its sheer beauty” - “in which the great Silesian poet of the seventeenth century reminds us that nature needs no justification for its sheer beauty. “The 2001 article became Guimarães' bibliometrically most successful.

The influence of pharmaceuticals on living beings is not only determined by pharmacodynamics , particularly the presence of receptors, but also by pharmacokinetics , the “fate” of pharmaceuticals in living tissue. This aspect was also examined in detail for the catecholamines and blood vessels in Porto. Metabolizing enzymes, namely monoamine oxidase and catechol-O-methyltransferase (COMT), as well as transporters for the passage through cell membranes, contributed to the removal of catecholamines from the extracellular space - and thus from the vicinity of the receptors and to the loss of effectiveness - but depending on the catecholamine and Blood vessel different.

One of the differences was that COMT inhibitors increased the effect of isoprenaline on β-adrenoceptors (and the subsequent relaxation of the blood vessels), but not the effect of noradrenaline on α-adrenoceptors (and the subsequent contraction of blood vessels). Conversely, inhibitors of the transport of noradrenaline to the sympathetic axon endings - a typical inhibitor is cocaine - increased the effect of noradrenaline on α- but not the effect of isoprenaline on β-adrenoceptors. Guimarães and his colleagues concluded that the density of COMT is greater in the "biophase" of the β-adrenoceptors than in the biophase of the α-adrenoceptors. Conversely, the density of cocaine-inhibitable transporters would have to be greater in the biophase of the α-adrenoceptors than in the biophase of the β-adrenoceptors. The hypothesis was supported by two articles in Naunyn-Schmiedeberg's Archives of Pharmacology , which were featured in a history of the journal. In 1982 Guimarães wrote in Trends in Pharmacological Sciences : “In blood vessels there are two biophases for sympathomimetics (which include catecholamines): one for the α-adrenoceptors, near the sympathetic axon terminals, where agonists mainly act is limited by transport into the axonal terminals; and one for the β-adrenoceptors, where the action of agonists is mainly limited by the COMT. ”The pharmacologists would have to reckon with a very inhomogeneous distribution of the catecholamines in the extracellular space instead of a homogeneous one as before - low concentration in the immediate vicinity of“ sites of loss ”, namely transporters and enzymes, considerably higher concentrations at a greater distance.

Much attention - Guimarães' bibliometrically third most successful article, at the same time his most successful original work with new experimental results - was a short communication about presynaptic β-adrenoceptors in the sympathetic nervous system, the activation of which increases the release of the sympathetic neurotransmitter noradrenaline. The receptors, activated by previously released noradrenaline, should increase the further release - a positive feedback that could never be verified experimentally, perhaps because the receptors of the subtype β 2 and thus are relatively insensitive to noradrenaline. Guimarães and co-workers enriched the sympathetic axon terminals with adrenaline, which has a strong effect on β 2 -adrenoceptors. In fact, this resulted in positive feedback: the beta blocker propranolol reduced the release. The authors concluded “that the introduction of adrenaline as a 'false transmitter' leads to the formation of a β-adrenoceptor-mediated positive feedback.” The interest in the discovery stems from the possibility here of a mechanism of the therapeutic effect of beta blockers in the arterial Find hypertension . In hypertension, adrenaline secreted from the adrenal medulla, accumulated in sympathetic axon endings, could create pathological positive feedback, and beta-blockers could prevent the resulting pathological excess release of the sympathetic transmitter.

Work on angiotensin II and adenosine , their receptors and their role in the development of arterial hypertension complete the research spectrum of the Pharmacological Institute of the Porto Medical Faculty during these years.

The Porto Meetings on Adrenergic Mechanisms

When the group found their big topic in Porto, they also started a series of similarly minded gatherings, the Porto Meetings on Adrenergic Mechanisms . The first meeting took place in 1970, with forty participants. Ten more meetings followed, in 1973, 1978, 1981, 1983, 1986, 1989, 1993, 1996, 2000 and 2003. The meetings were much smaller than the International Catecholamine Symposia, which began in 1958 . The abstract book of the 1993 Porto meeting contained 67 articles, the abstract book of the International Catecholamine Symposium 1992 in Amsterdam 728. The exchange of ideas was all the more intense. The visitors also fondly remembered what happened outside of science, "the hospitality of the Portuguese, the Coimbra - Fados Serafim Guimarães", the dinner with the mayor of Amarante in 1973, the unanimous desire for scopolamin or meclozin on the serpentine drive through the Douro -Tal 1989. "

Teaching

Serafim Guimarães' lectures were supplemented by the co- editing of the textbook Terapêutica Medicamentosa e Suas Bases Farmacológicas ( Medicines and their pharmacological foundations ). So far the following editions have been published:

  • 1st edition 1983, edited by Garrett and Osswald;
  • 2nd edition 1986, also edited by Garrett and Osswald;
  • 3rd edition 1999, edited by Garrett, Osswald and Guimarães;
  • 4th edition 2001, edited by Osswald and Guimarães;
  • 5th edition 2006, edited by Guimarães, Moura and Soares-da-Silva;
  • 6th edition 2014, also published by Guimarães, Moura and Soares-da-Silva. Porto, Verlag Porto Editora , ISBN 978-972-0-01794-9 .

Guimarães also wrote or co-wrote several chapters in the book, such as the Sistema adrenérgico chapter .

student

The following scientists, under the guidance of Guimarães, wrote the dissertation for their Ph.D. Developed.

At the Porto Medical Faculty:

  • Fernando Augusto Andrade de Abreu Brandão (1980)
  • Daniel Filipe Lima Moura (1988)
  • José Pedro Lopes Nunes (1996)
  • Manuel Joaquim Lopes Vaz da Silva (1996)
  • Rosa Sousa Martins da Rocha Begonha (1999)
  • Alberto Vieira da Mota (2004) -

At the Faculty of Pharmacy at the University of Porto:

  • Jorge Moreira Gonçalves (1991)
  • Jorge Alberto de Barros Brandão Proença (1991)
  • Helder Pinheiro (2003) -

At the Faculty of Pharmacy, Coimbra University :

  • Isabel Vitória Neves de Figueiredo Santos Pereira (1998).

further activities

From 1983 to 1984 Guimarães was Dean of the Porto Medical Faculty, Vice-Rector of the University from 1984 to 1985, founding member of the Federation of European Pharmacological Societies (EPHAR) from 1986 to 1988 , and President of the Sociedade Portuguesa de Farmacologia from 1995 to 1998 . From 1969 to 2000 he worked as the medical director of the Monfortinho Spa , from 1972 to 1995 as a scientific advisor to the Portuguese pharmaceutical company BIAL .

He is President of the Advisory Board of the Hospital de São João , the Clinic of the Medical Faculty of the University of Porto, and President of the Liga dos Amigos do São João , the Friends of the Hospital . He is a member of the body that exercises patronage over the Castelo da Feira , the fortress of Santa Maria da Feira dating back to pre-Roman times .

He used his talent for drawing for the above-mentioned book Retratos legendados . He presented the history of Castelo da Feira in the book Castelo de Santa Maria da Feira , printed in 1000 copies in 2008 , and his time in Angola in the book Entre duas Angolas published in 2018 .

References and comments

  1. ^ A b c Klaus Starke : The Porto meetings on adrenergic mechanisms . In: Journal of Autonomic Pharmacology . 17, No. 4, 1997, pp. 205-210. doi : 10.1046 / j.1365-2680.1997.00468.x .
  2. Some information about Guimarães' life and his students are taken from the Portuguese Wikipedia article Serafim Guimarães .
  3. ^ S. Guimarães, U. Trendelenburg: Deviation supersensitivity and inhibition of saturable sites of loss . In: Trends in Pharmacological Sciences . 6, 1985, pp. 371-374. doi : 10.1016 / 0165-6147 (85) 90175-0 .
  4. a b Seratim Guimarães: Retratos legendados - portraits in pictures and words . Universidade do Porto, Porto 2012. ISBN 978-989-746-002-9 . The pictures are handwritten drawings by Guimarães.
  5. ^ Sónia Machado: Encontros do Porto com a história da Farmacologia . In: Arquivos de Medicina - Revista de Ciência e Arte Médicas . 11, No. 6, 1997, pp. 376-383.
  6. José-Maria de Oliveira (director from 1920 to 1944), Alberto Malafaya-Baptista (director from 1944 to 1966), José Ruiz de Almeida Garrett (director from 1966 to 1987), Walter Osswald (director from 1987) followed in the institute management to 1990), Serafim Guimarães (1990 to 2005), finally Patrício Soares-da-Silva (since 2005). On Garrett see Serafim Guimarães (ed.): Homenagem a José Ruiz de Almeida Garrett. Postage, private printing 2001.
  7. J. Garrett, A. Malafaya-Baptista, W. Osswald: Effects of pronethalol on the cardiovascular actions of catecholamines during blockade by phenoxybenzamine . In: British Journal of Pharmacology . 27, No. 3, 1966, pp. 459-467. doi : 10.1111 / j.1476-5381.1966.tb01857.x .
  8. ^ S. Guimarães: Alpha excitatory, alpha inhibitory and beta inhibitory adrenergic receptors in the guinea-pig stomach . In: Archives internationales de Pharmacodynamie et de Thérapie . 179, No. 1, 1969, pp. 188-201. PMID 4390662 .
  9. ^ S. Guimarães, W. Osswald: Adrenergic receptors in the veins of the dog . In: European Journal of Pharmacology . 5, No. 2, 1969, pp. 188-201. doi : 10.1016 / 0014-2999 (69) 90021-1 .
  10. S. Guimarães, JP Nunes: The effectiveness of α 2 -adrenoceptor activation increases from the distal to the proximal part of the veins of canine limbs . In: British Journal of Pharmacology . 101, 1990, pp. 387-393. doi : 10.1111 / j.1476-5381.1990.tb12719.x .
  11. ^ Walter Osswald, Serafim Guimarães: Adrenergic mechanisms in blood vessels: morphological and pharmacological aspects . In: Reviews of Physiology, Biochemistry and Pharmacology . 96, 1983, pp. 53-122.
  12. ^ Serafim Guimarães, Daniel Moura: Vascular adrenoceptors: an update . In: Pharmacological Reviews . 53, No. 2, 2001, pp. 319-356. PMID 11356987 .
  13. ^ W. Osswald, S. Guimarães, A. Coimbra: The termination of action of catecholamines in the isolated venous tissue of the dog . In: Naunyn-Schmiedebergs Archive for Pharmacology . 269, No. 1, 1971, pp. 15-31. doi : 10.1007 / BF01422013 .
  14. ^ F. Brandão, S. Guimarães: Inactivation of endogenous noradrenalin released by electrical stimulation in vitro of dog saphenous vein. . In: Blood Vessels . 11, No. 1-2, 1974, pp. 45-54. doi : 10.1159 / 000157998 . PMID 4447847 .
  15. ^ S. Guimarães, MQ Paiva: The role played by the extraneuronal system in the disposition of noradrenaline and adrenaline in vessels . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 296, No. 3, 1977, pp. 279-287. doi : 10.1007 / BF00498694 .
  16. MQ Paiva, S. Guimarães: A comparative study of the uptake and metabolism of noradrenaline and adrenaline by the isolated saphenous vein of the dog . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 303, No. 3, 1978, pp. 221-228. doi : 10.1007 / BF00498047 . PMID 683349 .
  17. ^ Serafim Guimarães, Further study of the adrenoceptors of the saphenous vein of the dog: Influence of factors which interfere with the concentrations of agonists at the receptor level . In: European Journal of Pharmacology . 34, 1975, pp. 9-18. doi : 10.1016 / 0014-2999 (75) 90220-4 .
  18. ^ S. Guimarães, I. Azevedo, W. Cardoso, MC Oliveira: Relation between the amount of smooth muscle of venous tissue and the degree of supersensitivity to isoprenaline caused by inhibition of catechol-O-methyl transferase . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 286, No. 4, 1975, pp. 401-412. doi : 10.1007 / BF00506654 . PMID 1095935 .
  19. Robert Francis Furchgott coined the term “biophase” in 1955 for the tissue region in the immediate vicinity of the receptors: Robert F. Furchgott: The pharmacology of vascular smooth muscle . In: Pharmacological Reviews . 7, 1955, pp. 184-265, here p. 213. PMID 13245382 .
  20. ^ S. Guimarães, MQ Paiva: Two distinct adrenoceptor-biophases in the vasculature: One for α-and the other for β-agonists . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 316, No. 3, 1981, pp. 195-199. doi : 10.1007 / BF00505649 .
  21. S. Guimarães, MQ Paiva: Two different biophases for adrenaline released by electrical stimulation or tyramine from the sympathetic nerve endings of the dog saphenous vein . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 316, No. 3, 1981, pp. 200-204. doi : 10.1007 / BF00505650 . PMID 6265808 .
  22. ^ Klaus Starke: A history of Naunyn-Schmiedeberg's Archives of Pharmacology . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 358, No. 1, 1998, pp. 1-109, here p. 77. doi : 10.1007 / PL00005229 .
  23. S. Guimarães: Two adrenergic biophases in blood vessels . In: Trends in Pharmacological Sciences . 3, No. 1, 1982, pp. 159-161. doi : 10.1016 / 0165-6147 (82) 91069-0 .
  24. S. Guimarães, F. Brandão, MQ Paiva: A study of the adrenoceptor-mediated feedback mechanisms by using adrenaline as a false transmitter . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 305, No. 2, 1978, pp. 185-188. doi : 10.1007 / BF00508291 .
  25. K. 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. 11th edition, Munich, Elsevier GmbH 2013, page 153-189, here page 176. ISBN 978-3-437-16888-8
  26. ^ S. Guimarães, MQ Paiva, D. Moura: Different receptors for angiotensin II at pre- and postjunctional level of the canine mesenteric and pulmonary arteries . In: British Journal of Pharmacology . 124, No. 6, 1998, pp. 1207-1212. doi : 10.1038 / sj.bjp.0701959 . PMID 9720792 .
  27. Manuela Morato, Teresa Sousa, Serafim Guimarães, Daniel Moura, António Albino-Teixeira: The role of angiotensin II in hypertension due to adenosine receptors blockade . In: European Journal of Pharmacology . 455, No. 2-3, 2002, pp. 135-141. doi : 10.1016 / S0014-2999 (02) 02587-6 .
  28. Anne-Ulrike Trendelenburg, Angelika Meyer, Werner Klebroff, Serafim Guimarães, Klaus Starke: Crosstalk between presynaptic angiotensin receptors, bradykinin receptors and α 2 -autoreceptors in sympathetic neurons: a study in α 2 -adrenoceptor-deficient mice . In: British Journal of Pharmacology . 138, No. 8, 2003, pp. 1389-1402. doi : 10.1038 / sj.bjp.0705223 .
  29. Serafim Guimarães, Catarina Carneiro, Fernando Brandão, Helder Pinheiro, António Albino-Teixeira, Daniel Moura: A pharmacological differentiation between postjunctional (AT 1A ) and prejunctional (AT 1B ) angiotensin II receptors in the rabbit aorta . In: Naunyn-Schmiedeberg's Archives of Pharmacology . 270, No. 4, 2004, pp. 262-269. doi : 10.1007 / s00210-004-0977-7 .
  30. ^ Serafim Guimarães, Helder Pinheiro: Functional evidence that in the cardiovascular system AT 1 angiotensin II receptors are AT 1B prejunctionally and AT 1A postjunctionally . In: Cardiovascular Research . 67, 2005, pp. 208-215. doi : 10.1016 / j.cardiores.2005.04.015 .
  31. The two substances are antiemetics .
  32. Serafim Guimarães: Castelo de Santa Maria da Feira . Comissão de Vigilância do Castelo de Santa Maria da Feira, 2008.