Sakamoto C, Matozaki T, Nishisaki H, Konda Y, Nagao M, Nakano O
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Dig Dis Sci. 1990 Jul;35(7):873-8. doi: 10.1007/BF01536801.
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.
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。
