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胃肠激素的历史以及波兰在阐明其生物学特性及其与神经系统关系方面的贡献。

The history of gastrointestinal hormones and the Polish contribution to elucidation of their biology and relation to nervous system.

作者信息

Konturek P C, Konturek S J

机构信息

First Department of Medicine, University Erlangen-Nuremberg, Erlangen, Germany.

出版信息

J Physiol Pharmacol. 2003 Dec;54 Suppl 3:83-98.

Abstract

At the turn of XIX and XX century, the principal concept explaining the mechanism of secretory activity of the digestive glands was nervism proposed by I. P. Pavlov at Russian physiological school in St Petersburg, and this dogma was widely recognized for several years in other countries. The discovery of secretin in 1902 by W.B. Bayliss and E.H. Starling, and then of gastrin in 1906 by J.S. Edkins, emphasized the hormonal regulation of pancreatic and gastric secretion, respectively. In 1943, A.C. Ivy and E. Olberg discovered a hormone, which contracts the gallbladder - cholecystokinin (CCK), while A. Harper and H.S. Raper described another hormone, pancreozymin, which stimulated pancreatic enzymes. It required over twenty years, however, for these and many other hormones to be identified, purified and synthesized due to the extensive work of several teams including R. Gregory, G. Dockray and Kenner of the UK; J. Rehfeld of Denmark and E. Wunsch of Germany for their work on gastrin; E. Jorpes and V. Mutt of Sweden and N. Yahaihara of Japan for their work on secretin and other GI hormones including, CCK, vasoactive intestinal peptide (VIP), gastric inhibitory peptide (GIP), motilin, gastrin-releasing peptide (GRP) and others peptides. CCK and pancreaozymin were found by E. Jorpes and V. Mutt to represent structurally a common messenger for pancreatico-biliary secretion. This rapid development of GI endocrinology in the 1960s and 1970s could be attributed to the application of peptide biochemistry in characterizing various peptide hormones. The technique of radioimmunoassay by S.A. Berson and R.S. Yalow in 1959 measured minute amounts of hormones in the circulation and tissue, and the technique of immunocytochemistry detected the cellular origin of these hormones. Further progress in molecular biology led to sequencing GI hormones and their prohormones, and opened a new area of investigation for the physiological role of these hormones in the mechanism of digestive gland secretion, motility of gastrointestinal tract, visceral blood flow, tissue growth and integrity in health, as well as in various digestive diseases. Overall, apparent divergent concepts, the nervous control (Pavlov) and hormonal control (Bayliss and Starling), greatly facilitated the elucidation of the interacting neurohormones during the cephalic, gastric, and intestinal phases of gastric and pancreatic secretion in health and digestive diseases. Although Polish contributions in the early phase of GI endocrinology concerned mostly gastric inhibitory hormones such as enterogastrone and urogastrone, major Polish traces can be detected in the elucidation of origin and physiological role and pathological involvement of gastrin, CCK, secretin, motilin, gastric inhibitory peptide and the most recent additions of enterohormones such as epidermal growth factor, somatostatin, leptin or ghrelin. Major achievements have been obtained in gastric and colorectal cancerogenesis involving gastrin and its precursor, progastrin.

摘要

在19世纪末20世纪初,解释消化腺分泌活动机制的主要概念是由圣彼得堡俄罗斯生理学派的I. P. 巴甫洛夫提出的神经论,这一教条在其他国家被广泛认可了数年。1902年W. B. 贝利斯和E. H. 斯塔林发现了促胰液素,随后1906年J. S. 埃金斯发现了胃泌素,分别强调了胰腺和胃分泌的激素调节。1943年,A. C. 艾维与E. 奥尔伯格发现了一种能使胆囊收缩的激素——缩胆囊素(CCK),而A. 哈珀和H. S. 雷珀描述了另一种激素——促胰酶素,它能刺激胰腺酶的分泌。然而,由于包括英国的R. 格雷戈里、G. 多克雷和肯纳;丹麦的J. 雷费尔德以及德国的E. 温施在内的几个团队在胃泌素方面的大量工作;瑞典的E. 约佩斯和V. 穆特以及日本的N. 矢原原在促胰液素和包括CCK、血管活性肠肽(VIP)、胃抑制肽(GIP)、胃动素、胃泌素释放肽(GRP)等其他胃肠激素方面的工作,这些激素以及许多其他激素的鉴定、纯化和合成花了二十多年时间。E. 约佩斯和V. 穆特发现CCK和促胰酶素在结构上代表胰胆分泌的一种共同信使。20世纪60年代和70年代胃肠内分泌学的这一快速发展可归因于肽生物化学在表征各种肽激素方面的应用。1959年S. A. 伯森和R. S. 亚洛发明的放射免疫测定技术可测量循环和组织中微量的激素,免疫细胞化学技术则可检测这些激素的细胞来源。分子生物学的进一步发展导致胃肠激素及其前体激素的测序,并为这些激素在消化腺分泌机制、胃肠道运动、内脏血流、组织生长以及健康和各种消化系统疾病中的生理作用开辟了一个新的研究领域。总体而言,明显不同的概念,即神经控制(巴甫洛夫)和激素控制(贝利斯和斯塔林),极大地促进了对健康和消化系统疾病中胃和胰腺分泌的头期、胃期和肠期相互作用的神经激素的阐明。尽管波兰在胃肠内分泌学早期的贡献主要涉及肠抑胃素和尿抑胃素等胃抑制激素,但在胃泌素、CCK、促胰液素、胃动素、胃抑制肽以及最近添加的肠激素如表皮生长因子、生长抑素、瘦素或胃饥饿素的起源、生理作用和病理参与的阐明中可以发现波兰的重要踪迹。在涉及胃泌素及其前体胃泌素原的胃癌和结直肠癌发生方面已经取得了重大成就。

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