Schusdziarra V, Bender H, Pfeffer A, Pfeiffer E F
Regul Pept. 1984 Apr;8(3):189-98. doi: 10.1016/0167-0115(84)90060-0.
Recently we have shown the release of bombesin-like immunoreactivity (BLI) from the isolated perfused rat stomach. In these experiments we have shown that BLI secretion is stimulated by acetylcholine. Gastric inhibitory peptide (GIP) exerts an inhibitory effect which is dependent on the intraluminal pH. The present study was designed to examine further the exact cholinergic mechanisms and to study the interaction between cholinergic and histaminergic mechanisms as well as the effect of the intraluminal pH. Acetylcholine elicited a dose-dependent increase in BLI and gastrin secretion (10(-6) M and 2 X 10(-6)M), whereas somatostatin release was suppressed at luminal pH 7. Blockade of muscarinic cholinergic receptors by atropine (10(-5)M) and nicotinic cholinergic receptors by hexamethonium (10(-5) M) abolished the effect of acetylcholine on all three peptides. Reduction of the intraluminal pH to 2 also abolished acetylcholine-induced stimulation of BLI and gastrin secretion and the inhibition of somatostatin secretion. Changes of intraluminal pH per se had no effect on the secretion of either peptide. Somatostatin (10(-7) M) reduced both BLI and gastrin secretion during stimulation with acetylcholine. The addition of the H2-receptor antagonist cimetidine (10(-5) M) abolished the effect of both doses of acetylcholine on BLI and somatostatin secretion and also the effect of the lower dose of acetylcholine (10(-6) M) on gastrin secretion during luminal pH 7. At luminal pH 2 cimetidine did not alter BLI and somatostatin secretion in response to acetylcholine, however, gastrin release was augmented in the presence of cimetidine. These data demonstrate that the effect of acetylcholine on BLI, gastrin, and somatostatin secretion is mediated by muscarinic and nicotinic cholinergic receptors and also by histamine H2-receptors. Somatostatin inhibits cholinergically induced BLI secretion. The cholinergic effects on BLI, somatostatin and gastrin secretion are abolished during an acidic intragastric pH. In this isolated perfused rat stomach model the inhibitory effect of intraluminal acid on gastrin secretion is, at least in part, mediated by H2-receptors. This suggests that the secretion of bombesin, a potential peptidergic neurotransmitter is modulated by neural, endocrine and local tissue factors and also by alterations of intragastric pH.
最近我们已证明，在离体灌注的大鼠胃中会释放出蛙皮素样免疫反应性物质（BLI）。在这些实验中我们已表明，乙酰胆碱可刺激BLI的分泌。胃抑肽（GIP）发挥抑制作用，该作用取决于管腔内的pH值。本研究旨在进一步探究确切的胆碱能机制，并研究胆碱能与组胺能机制之间的相互作用以及管腔内pH值的影响。乙酰胆碱引起BLI和胃泌素分泌呈剂量依赖性增加（10⁻⁶ M和2×10⁻⁶ M），而在管腔pH值为7时，生长抑素的释放受到抑制。阿托品（10⁻⁵ M）阻断毒蕈碱型胆碱能受体以及六甲铵（10⁻⁵ M）阻断烟碱型胆碱能受体，均消除了乙酰胆碱对这三种肽的作用。将管腔内pH值降至2也消除了乙酰胆碱诱导的BLI和胃泌素分泌的刺激以及生长抑素分泌的抑制。管腔内pH值本身的变化对任何一种肽的分泌均无影响。生长抑素（10⁻⁷ M）在乙酰胆碱刺激期间减少了BLI和胃泌素的分泌。添加H₂受体拮抗剂西咪替丁（10⁻⁵ M）消除了两种剂量的乙酰胆碱对BLI和生长抑素分泌的作用，以及在管腔pH值为7时较低剂量乙酰胆碱（10⁻⁶ M）对胃泌素分泌的作用。在管腔pH值为2时，西咪替丁并未改变乙酰胆碱刺激引起的BLI和生长抑素分泌，然而，在西咪替丁存在的情况下，胃泌素释放增加。这些数据表明，乙酰胆碱对BLI、胃泌素和生长抑素分泌的作用是由毒蕈碱型和烟碱型胆碱能受体以及组胺H₂受体介导的。生长抑素抑制胆碱能诱导的BLI分泌。在胃内酸性pH值期间，胆碱能对BLI、生长抑素和胃泌素分泌的作用被消除。在这个离体灌注的大鼠胃模型中，管腔内酸对胃泌素分泌的抑制作用至少部分是由H₂受体介导的。这表明，作为一种潜在肽能神经递质的蛙皮素的分泌受到神经、内分泌和局部组织因子以及胃内pH值变化的调节。
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