Schubert M L
Department of Medicine, Medical College of Virginia, Richmond.
Gastroenterology. 1991 May;100(5 Pt 1):1195-200.
The mechanism of action of vasoactive intestinal polypeptide on gastric acid secretion was examined in the isolated, luminally perfused mouse stomach. Vasoactive intestinal polypeptide caused a weak, transient increase in basal and histamine-stimulated acid secretion and a sustained increase in somatostatin secretion. The sustained increase in somatostatin despite return of acid to basal levels indicated that somatostatin secretion was a direct response to vasoactive intestinal polypeptide and not mediated by intraluminal acidification. The increase in somatostatin secretion was partly responsible for the weak, transient nature of the acid response since incubation with pertussis toxin, which is known to block the inhibitory effect of exogenous and endogenous somatostatin, converted the acid response to a sustained increase throughout the period of stimulation. The inhibitory influence of somatostatin was confirmed with selective vasoactive intestinal polypeptide antagonists. The antagonists inhibited vasoactive intestinal polypeptide-induced somatostatin secretion but caused a sustained increase in acid secretion. The pattern of response implied that somatostatin secretion was more sensitive than acid secretion to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide antagonists and that suppression of somatostatin eliminated the main inhibitory influence on acid secretion. In addition, both vasoactive intestinal polypeptide antagonists inhibited basal somatostatin secretion, implying that input from tonically active vasoactive intestinal polypeptide neurons is responsible, at least in part, for basal somatostatin secretion.
在分离的、经腔内灌注的小鼠胃中研究了血管活性肠肽对胃酸分泌的作用机制。血管活性肠肽使基础胃酸分泌和组胺刺激的胃酸分泌出现微弱、短暂的增加，并使生长抑素分泌持续增加。尽管胃酸分泌恢复到基础水平，但生长抑素仍持续增加，这表明生长抑素分泌是对血管活性肠肽的直接反应，而非由腔内酸化介导。生长抑素分泌的增加部分解释了胃酸反应微弱、短暂的特性，因为与已知可阻断外源性和内源性生长抑素抑制作用的百日咳毒素共同孵育后，在整个刺激期间胃酸反应转变为持续增加。用选择性血管活性肠肽拮抗剂证实了生长抑素的抑制作用。这些拮抗剂抑制血管活性肠肽诱导的生长抑素分泌，但导致胃酸分泌持续增加。这种反应模式表明，生长抑素分泌对血管活性肠肽和血管活性肠肽拮抗剂比胃酸分泌更敏感，并且生长抑素的抑制作用消除了对胃酸分泌的主要抑制影响。此外，两种血管活性肠肽拮抗剂均抑制基础生长抑素分泌，这意味着来自具有紧张性活性的血管活性肠肽神经元的输入至少部分负责基础生长抑素分泌。
