STIMULUS-SECRETION COUPLING - CONCEPT AND CLUES FROM CHROMAFFIN AND OTHER CELLS
STIMULUS-SECRETION COUPLING - CONCEPT AND CLUES FROM CHROMAFFIN AND OTHER CELLS
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DOI：
10.1111/j.1476-5381.1968.tb08474.x
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发表时间：
1968-01-01
影响因子：
7.3
通讯作者：
DOUGLAS, WW
中科院分区：
文献类型：
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作者：
DOUGLAS, WW
对约翰·加德杜姆令人惊讶的丰硕药理学生涯的主要影响之一是他在汉普斯特德的国家医学研究所的早期接触到了生理学和药理学之间的边缘学科，亨利·戴尔将其称为自我药理学。在汉普斯特德和他的一生中，加德杜姆的实验主要涉及从组织中提取的药理活性物质。他在这一领域的贡献太多了，不能在这里一一列举，但我想提醒你几个，它们说明了他工作的主题。你应该还记得，是加德姆和美国冯·欧拉(1931)一起发现了P物质。也是加德姆和张(1933)证明了交感神经链中含有丰富的具有乙酰胆碱生理特性的物质，并提出了这样的观点：“鉴于乙酰胆碱对神经节细胞的刺激作用，它可能参与了冲动的正常传递。”这一发现反过来又导致了他与Feldberg(1934)一起进行的实验，展示了受刺激的颈上神经节释放乙酰胆碱，这一实验成为神经元通过化学手段相互交流的概念的基石。当然，加德姆将继续在这种自我药理的静脉中度过他的一生，例如，有助于了解肾上腺素能神经和其他金字塔类物质的生理学和药理学知识，如组胺、5-羟色胺和缓激肽。他的众多贡献之一是1952年在大脑中发现了5-羟色胺(见Amin，Crawford&Gadum1954)。紧随其后的是证明麦角酸二乙胺(LSD)是5-羟色胺的有效拮抗剂，并暗示LSD的精神影响可能归因于干扰5-羟色胺的正常作用(Gadum1953；Amin等人，1954)。现在很明显，这些实验和从中得出的结论，有力地推动了大脑内递质的研究和精神药理学领域的发展。因此，在第一次加德姆纪念讲座中，主题应该是一个自我药理学的主题，加德姆纪念基金的受托人
One of the main influences on John Gaddum's astonishingly fruitful career in pharmacology was his early exposure, at theNational Institute for Medical Research in Hampstead, to that borderline discipline between physiology and pharmacology that Henry Dale was to term autopharmacology. At Hampstead, and throughout his life, Gaddum's experiments were concerned mainly with pharmacologically active substances extractable from tissues. His contributions in this field are too many to list here, but I should like to remind you of a few that illustrate the main theme of his work. It was Gaddum, you will remember, who, along with US von Euler (1931), discovered substance P. It was Gaddum, too, who demonstrated, with Chang (1933), that the sympathetic chain was rich in a substance with the physiological properties of acetylcholine and who put forward the idea that" acetyl-choline might play a partin the normal transmission of impulses having in view its stimulating actions on ganglion cells." This finding inturn led him to the experiment, with Feldberg (1934), demonstrating release of acetylcholine from the stimulated superior cervical ganglion, an experiment that became the cornerstone of the concept that neurones communicate with one another by chemical means. And, of course, Gaddum was to continue throughout his life in this autopharmacological vein contributing, for example, to knowledge of the physiology and pharmacology of the transmitter substance of adrenergic nerves and other autacoids such as histamine, 5-hydroxytryptamine and bradykinin. Among his many contributions was the discovery, in 1952, of5-hydroxytryptamine within the brain (see Amin, Crawford & Gaddum, 1954). This was shortly followed by the demonstration that lysergic acid diethylamide (LSD) is a potent antagonist of 5-hydroxytryptamine and by the suggestion that LSD might owe its mental effects to interference with the normal action of 5-hydroxytryptamine (Gaddum, 1953; Amin et al., 1954). It is now evidentthat these experiments, and the conclusions drawn from them, gave powerful impetus to the study of transmitter substances within the brain and to the development of the field of psychopharmacology. In this first Gaddum Memorial Lecture it is, then, appropriate that the topic be an autopharmacological one, and the Trustees of the Gaddum Memorial Fund