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TLQP-21,一种 VGF 衍生肽,在大鼠胃分泌抑制作用中的机制特征。

Characterization of the mechanisms involved in the gastric antisecretory effect of TLQP-21, a vgf-derived peptide, in rats.

机构信息

Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Via Vanvitelli, 32, 20129, Milan, Italy.

出版信息

Amino Acids. 2012 Apr;42(4):1261-8. doi: 10.1007/s00726-010-0818-6. Epub 2010 Dec 4.

DOI:10.1007/s00726-010-0818-6
PMID:21132337
Abstract

TLQP-21, a vgf-derived peptide modulates gastric emptying and prevents ethanol-induced gastric lesions in rats. However, it remains to be studied whether or not TLQP-21 affects gastric acid secretion. In this study, we evaluated the effects of central (0.8-8 nmol/rat) or peripheral (48-240 nmol/kg, intraperitoneally) TLQP-21 administration on gastric acid secretion in pylorus-ligated rats. The mechanisms involved in such activity were also examined. Central TLQP-21 injection significantly reduced gastric acid volume and dose-dependently inhibited total acid output (ED(50) = 2.71 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 antisecretory activity was prevented by cysteamine (300 mg/kg, subcutaneously), a depletor of somatostatin, by indomethacin (0.25 mg/rat, intracerebroventricularly), a non-selective cyclooxygenase inhibitor, and by functional ablation of sensory nerves by capsaicin. We conclude that TLQP-21 could be considered a new member of the large group of regulatory peptides affecting gastric acid secretion. The central inhibitory effect of TLQP-21 on gastric acid secretion is mediated by endogenous somatostatin and prostaglandins and requires the integrity of sensory nerve fibres.

摘要

TLQP-21,一种源自 vgf 的肽,可调节胃排空并预防大鼠乙醇诱导的胃损伤。然而,TLQP-21 是否影响胃酸分泌仍有待研究。在这项研究中,我们评估了中枢(0.8-8 nmol/rat)或外周(48-240 nmol/kg,腹腔内)TLQP-21 给药对幽门结扎大鼠胃酸分泌的影响。还研究了这种活性涉及的机制。中枢 TLQP-21 注射显著减少胃酸量,并呈剂量依赖性抑制总酸分泌(ED50 = 2.71 nmol),而外周 TLQP-21 给药则没有影响。TLQP-21 的抗分泌活性被半胱胺(300 mg/kg,皮下注射)、一种生长抑素耗竭剂、非选择性环加氧酶抑制剂吲哚美辛(0.25 mg/rat,脑室内注射)和辣椒素(capsaicin)对感觉神经的功能消融所阻止。我们得出结论,TLQP-21 可以被认为是影响胃酸分泌的一大类调节肽中的新成员。TLQP-21 对胃酸分泌的中枢抑制作用是通过内源性生长抑素和前列腺素介导的,并且需要感觉神经纤维的完整性。

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