Buchan A M, Meloche R M, Kwok Y N, Kofod H
Department of Physiology, University of British Columbia, Vancouver.
Gastroenterology. 1993 May;104(5):1414-9. doi: 10.1016/0016-5085(93)90350-l.
Both secretin and cholecystokinin (CCK) inhibit gastric acid secretion. However, their mode of action has yet to be determined. A newly developed primary culture of human antral epithelial cells has been used to examine the effect of secretin and cholecystokinin on somatostatin release.
Normal human antral epithelial cell cultures enriched for D cells were maintained in culture for 2 days before release studies.
Native human secretin at 10(-8) mol/L stimulated somatostatin release threefold. Porcine secretin and the secretin analogs, Tyr10 human secretin, Tyr13 porcine secretin, and Tyr10,13 porcine secretin were equipotent to native human secretin. CCK stimulated somatostatin release with the greatest response (eight times basal) at 10(-7) mol/L. The response to CCK was inhibited in a competitive manner by the addition of the benzodiazepine analog, MK-329. Addition of secretin in the presence of 10(-8) mol/L CCK resulted in a potentiation of somatostatin release, with the greatest response at 10(6) mol/L secretin, resulting in a 12-fold increase above basal.
The stimulation observed after the addition of CCK was the result of activation of the CCK-A receptor subtype. The secretin receptor resembles that of the pancreatic D cells and acts through increasing intracellular cyclic adenosine monophosphate levels. Finally, these data indicate that the inhibitory action of CCK and secretin on gastric acid secretion may result from a synergistic action on antral D cells to release somatostatin, which in turn decreases antral gastrin release.
促胰液素和胆囊收缩素（CCK）均能抑制胃酸分泌。然而，它们的作用方式尚未确定。一种新建立的人胃窦上皮细胞原代培养体系已被用于研究促胰液素和胆囊收缩素对生长抑素释放的影响。
在进行释放研究前，将富含D细胞的正常人胃窦上皮细胞培养物维持培养2天。
10⁻⁸mol/L的天然人促胰液素刺激生长抑素释放增加了三倍。猪促胰液素和促胰液素类似物，即酪氨酸¹⁰人促胰液素、酪氨酸¹³猪促胰液素以及酪氨酸¹⁰,¹³猪促胰液素与天然人促胰液素具有同等效力。CCK在10⁻⁷mol/L时刺激生长抑素释放的反应最为强烈（是基础水平的八倍）。添加苯二氮䓬类似物MK - 329可竞争性抑制对CCK的反应。在存在10⁻⁸mol/L CCK的情况下添加促胰液素会导致生长抑素释放增强，在促胰液素浓度为10⁻⁶mol/L时反应最为强烈，导致比基础水平增加12倍。
添加CCK后观察到的刺激是CCK - A受体亚型激活的结果。促胰液素受体与胰腺D细胞的受体相似，通过增加细胞内环磷酸腺苷水平发挥作用。最后，这些数据表明CCK和促胰液素对胃酸分泌的抑制作用可能源于对胃窦D细胞释放生长抑素的协同作用，进而减少胃窦胃泌素的释放。
