胆囊收缩素受体拮抗剂对胆囊收缩素刺激的豚鼠离体胃主细胞胃蛋白酶原分泌及钙增加的影响。

Effects of CCK-receptor antagonists on CCK-stimulated pepsinogen secretion and calcium increase in isolated guinea pig gastric chief cells.

作者信息

Sakamoto C, Matozaki T, Nishisaki H, Konda Y, Nagao M, Nakano O

机构信息

Second Department of Internal Medicine, Kobe University School of Medicine, Japan.

出版信息

Dig Dis Sci. 1990 Jul;35(7):873-8. doi: 10.1007/BF01536801.

DOI:10.1007/BF01536801

PMID:2364841

Abstract

The effects of CCK-receptor antagonists such as dibutyryl cyclic GMP (dbcGMP), L-364,718, and CR1409 on COOH-terminal octapeptide of CCK (CCK-8)-stimulated chief cell responses were examined using isolated guinea pig gastric chief cells. L-364,718 and CR1409 inhibited CCK-8-stimulated pepsinogen secretion over the same concentration range as they inhibited CCK-8-stimulated increases in intracellular Ca2+ concentration ([Ca2+]i), respectively. Schild analysis of the CCK dose-response curve indicates that L-364,718 and CR1409 exert their inhibitory effects on CCK-8-stimulated chief cell responses in a competitive manner. By contrast, dbcGMP inhibited not only CCK-8- but also carbachol-stimulated pepsinogen secretion. Furthermore, dbcGMP inhibited CCK-8-stimulated pepsinogen secretion more potently than the increases in [Ca2+]i. These results suggest that L-364,718 and CR1409 act as CCK-receptor antagonists, but dbcGMP has another inhibitory effect on pepsinogen secretion in addition to the effect as a CCK-receptor antagonist in guinea pig gastric chief cells.

摘要

使用分离的豚鼠胃主细胞，研究了胆囊收缩素（CCK）受体拮抗剂，如二丁酰环鸟苷酸（dbcGMP）、L-364,718和CR1409对CCK羧基末端八肽（CCK-8）刺激的主细胞反应的影响。L-364,718和CR1409在与它们分别抑制CCK-8刺激的细胞内钙离子浓度（[Ca2+]i）升高相同的浓度范围内，抑制CCK-8刺激的胃蛋白酶原分泌。对CCK剂量反应曲线的Schild分析表明，L-364,718和CR1409以竞争性方式对CCK-8刺激的主细胞反应发挥抑制作用。相比之下，dbcGMP不仅抑制CCK-8刺激的胃蛋白酶原分泌，还抑制卡巴胆碱刺激的胃蛋白酶原分泌。此外，dbcGMP抑制CCK-8刺激的胃蛋白酶原分泌的效力比抑制[Ca2+]i升高的效力更强。这些结果表明，L-364,718和CR1409作为CCK受体拮抗剂起作用，但在豚鼠胃主细胞中，dbcGMP除了作为CCK受体拮抗剂发挥作用外，对胃蛋白酶原分泌还有另一种抑制作用。