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血清素与超越——纪念曼弗雷德·格特(1939-2019)。

Serotonin and beyond-a tribute to Manfred Göthert (1939-2019).

机构信息

Institute of Pharmacology and Toxicology, University of Bonn, Venusberg-Campus 1, 53105, Bonn, Germany.

Merz Pharmaceuticals, Frankfurt/Main, Germany.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2021 Sep;394(9):1829-1867. doi: 10.1007/s00210-021-02083-5. Epub 2021 May 15.


DOI:10.1007/s00210-021-02083-5
PMID:33991216
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8376721/
Abstract

Manfred Göthert, who had served Naunyn-Schmiedeberg's Arch Pharmacol as Managing Editor from 1998 to 2005, deceased in June 2019. His scientific oeuvre encompasses more than 20 types of presynaptic receptors, mostly on serotoninergic and noradrenergic neurones. He was the first to identify presynaptic receptors for somatostatin and ACTH and described many presynaptic receptors, known from animal preparations, also in human tissue. In particular, he elucidated the pharmacology of presynaptic 5-HT receptors. A second field of interest included ligand-gated and voltage-dependent channels. The negative allosteric effect of anesthetics at peripheral nACh receptors is relevant for the peripheral clinical effects of these drugs and modified the Meyer-Overton hypothesis. The negative allosteric effect of ethanol at NMDA receptors in human brain tissue occurred at concentrations found in the range of clinical ethanol intoxication. Moreover, the inhibitory effect of gabapentinoids on P/Q Ca channels and the subsequent decrease in AMPA-induced noradrenaline release may contribute to their clinical effect. Another ligand-gated ion channel, the 5-HT receptor, attracted the interest of Manfred Göthert from the whole animal via isolated preparations down to the cellular level. He contributed to that molecular study in which 5-HT receptor subtypes were disclosed. Finally, he found altered pharmacological properties of 5-HT receptor variants like the Arg219Leu 5-HT receptor (which was also shown to be associated with major depression) and the Phe124Cys 5-HT receptor (which may be related to sumatriptan-induced vasospasm). Manfred Göthert was a brilliant scientist and his papers have a major impact on today's pharmacology.

摘要

曼弗雷德·戈尔特(Manfred Göthert)曾于 1998 年至 2005 年担任瑙恩-施密德贝格药物学档案的执行编辑,已于 2019 年 6 月去世。他的科学著作涵盖了 20 多种类型的突触前受体,主要是在 5-羟色胺能和去甲肾上腺素能神经元上。他首次鉴定了生长抑素和促肾上腺皮质激素的突触前受体,并描述了许多在动物制剂中已知的突触前受体,也存在于人体组织中。特别是,他阐明了突触前 5-羟色胺受体的药理学。他的第二个研究领域包括配体门控和电压依赖性通道。麻醉药在外周烟碱型乙酰胆碱受体上的负变构效应与这些药物的外周临床效应有关,并修改了梅耶-奥弗顿假说。在人类脑组织中,NMDA 受体上的乙醇负变构效应发生在临床乙醇中毒范围内的浓度。此外,加巴喷丁类药物对 P/Q Ca 通道的抑制作用以及随后减少 AMPA 诱导的去甲肾上腺素释放,可能有助于它们的临床效果。另一种配体门控离子通道,5-羟色胺受体,从整体动物通过分离制剂吸引了曼弗雷德·戈尔特的兴趣,一直到细胞水平。他对该分子研究做出了贡献,揭示了 5-羟色胺受体亚型。最后,他发现了 5-羟色胺受体变体的药理学特性发生了改变,如 Arg219Leu 5-羟色胺受体(也被证明与重度抑郁症有关)和 Phe124Cys 5-羟色胺受体(可能与舒马曲坦诱导的血管痉挛有关)。曼弗雷德·戈尔特是一位杰出的科学家,他的论文对当今药理学产生了重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1fe/8376721/b471f3e8901c/210_2021_2083_Fig12_HTML.jpg
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本文引用的文献

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Serotonin discovery and stepwise disclosure of 5-HT receptor complexity over four decades. Part II. Some contributions of Manfred Göthert.

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