Effects of CCK-receptor antagonists on CCK-stimulated pepsinogen secretion and calcium increase in isolated guinea pig gastric chief cells.
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.
Sakamoto
C
C
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Matozaki
T
T
Nishisaki
H
H
Konda
Y
Y
Nagao
M
M
Nakano
O
O
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010435:Pepsinogens / Q000378:metabolism*; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology
D001570:Benzodiazepinones; D010435:Pepsinogens; D011949:Receptors, Cholecystokinin; D003995:Dibutyryl Cyclic GMP; D002766:Cholecystokinin; D011377:Proglumide; D020109:Devazepide; C048181:lorglumide; D012844:Sincalide; D002118:Calcium