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向大鼠迷走神经背侧复合体微量注射外源性生长抑素可通过生长抑素受体-2抑制胰腺分泌。

Microinjection of exogenous somatostatin in the dorsal vagal complex inhibits pancreatic secretion via somatostatin receptor-2 in rats.

作者信息

Liao Zhuan, Li Zhao-Shen, Lu Yan, Wang Wei-Zhong

机构信息

Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

出版信息

Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G746-52. doi: 10.1152/ajpgi.00174.2006. Epub 2006 Nov 30.

Abstract

Previous studies have suggested that somatostatin inhibits pancreatic secretion at a central vagal site, and the dorsal vagal complex (DVC) is involved in central feedback inhibition of the exocrine pancreas. The aim of this study was to investigate the effect of exogenous somatostatin in the DVC on pancreatic secretion and the somatostatin receptor subtype(s) responsible for the effect. The effects of somatostatin microinjected into the DVC on pancreatic secretion stimulated by cholecystokinin octapeptide (CCK-8) or 2-deoxy-d-glucose (2-DG) were examined in anesthetized rats. To investigate the somatostatin inhibitory action site, a somatostatin receptor antagonist [SRA; cyclo(7-aminoheptanoyl-Phe-d-Trp-Lys-Thr)] was microinjected into the DVC before intravenous infusion of somatostatin and CCK-8/2-DG. The effects of injection of a somatostatin receptor-2 agonist (seglitide) and combined injection of somatostatin and a somatostatin receptor-2 antagonist (CYN 154806) in the DVC on the pancreatic secretion were also investigated. Somatostatin injected into the DVC significantly inhibited pancreatic secretion evoked by CCK-8 or 2-DG in a dose-dependent manner. SRA injected into the DVC completely reversed the inhibitory effect of intravenous administration of somatostatin. Seglitide injected into the DVC also inhibited CCK-8/2-DG-induced pancreatic protein secretion. However, combined injection of somatostatin and CYN 154806 did not affect the CCK-8/2-DG-induced pancreatic secretion. Somatostatin in the DVC inhibits pancreatic secretion via somatostatin receptor-2, and the DVC is the action site of somatostatin for its inhibitory effect.

摘要

以往研究表明,生长抑素在中枢迷走神经部位抑制胰腺分泌,背侧迷走神经复合体(DVC)参与胰腺外分泌的中枢反馈抑制。本研究旨在探讨DVC中外源性生长抑素对胰腺分泌的影响以及介导该效应的生长抑素受体亚型。在麻醉大鼠中,研究了向DVC微量注射生长抑素对八肽胆囊收缩素(CCK-8)或2-脱氧-D-葡萄糖(2-DG)刺激的胰腺分泌的影响。为研究生长抑素的抑制作用位点,在静脉输注生长抑素和CCK-8/2-DG之前,向DVC微量注射生长抑素受体拮抗剂[SRA;环(7-氨基庚酰-Phe-d-Trp-Lys-Thr)]。还研究了向DVC注射生长抑素受体-2激动剂(司美格鲁肽)以及联合注射生长抑素和生长抑素受体-2拮抗剂(CYN 154806)对胰腺分泌的影响。向DVC注射生长抑素以剂量依赖性方式显著抑制CCK-8或2-DG诱发的胰腺分泌。向DVC注射SRA完全逆转了静脉注射生长抑素的抑制作用。向DVC注射司美格鲁肽也抑制了CCK-8/2-DG诱导的胰腺蛋白质分泌。然而,联合注射生长抑素和CYN 154806并不影响CCK-8/2-DG诱导的胰腺分泌。DVC中的生长抑素通过生长抑素受体-2抑制胰腺分泌,且DVC是生长抑素发挥抑制作用的作用位点。

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