Effects of dibutyryl guanosine 3',5'-cyclic monophosphate and sodium nitroprusside in pepsinogen secretion from guinea pig chief cells with respect to intracellular Ca2+.
Both Ca2+ and adenosine 3',5'-cyclic monophosphate act as intracellular second messengers in pepsinogen secretion from chief cells. However, the role of intracellular guanosine 3',5'-cyclic monophosphate (cGMP) in this process has not been defined. Although dibutyryl cGMP (dbcGMP), a membrane-permeable derivative of cGMP, has been shown to inhibit pepsinogen secretion only stimulated by cholecystokinin (CCK), the intracellular mechanism of this effect remains unclear. We evaluated the role of intracellular cGMP in pepsinogen secretion from monolayer cultured guinea pig chief cells using dbcGMP and sodium nitroprusside, both of which increase intracellular cGMP. Dibutyryl cGMP and sodium nitroprusside have now been shown to inhibit pepsinogen secretion induced by not only CCK octapeptide but also carbamylcholine chloride and ionomycin in a dose-dependent manner. Furthermore, dbcGMP reduced the increase in intracellular free Ca2+ concentration induced by carbamylcholine chloride, CCK octapeptide, and ionomycin. These results suggest that intracellular cGMP may inhibit pepsinogen secretion by reducing the intracellular free Ca2+ concentration.
Okayama
N
N
First Department of Internal Medicine, Nagoya City University Medical School, Japan.
Itoh
M
M
Joh
T
T
Miyamoto
T
T
Takeuchi
T
T
Moriyama
A
A
Kato
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D015759:Ionomycin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D010435:Pepsinogens / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology
D010435:Pepsinogens; D009599:Nitroprusside; D003995:Dibutyryl Cyclic GMP; D015759:Ionomycin; D002217:Carbachol; D012844:Sincalide; D002118:Calcium