Carbachol inhibits stimulant-induced increases in fundic D-cell cytosolic Ca2+ concentration.
We undertook these studies to examine the mechanisms by which carbachol inhibits somatostatin release. For these studies, we utilized cultured D-cells isolated from the canine gastric fundus. Carbachol inhibited somatostatin release induced by both pentagastrin and 12-O-tetradecanoyl-phorbol-13-acetate but did not alter the redistribution of protein kinase C induced by these agents. In contrast, carbachol diminished the increase in D-cell cytosolic free calcium levels ([Ca2+]i) induced by pentagastrin, and this effect was no longer evident after pretreatment of D-cells with pertussis toxin. Although carbachol by itself had no effect on [Ca2+]i, after pretreatment of D-cells with pertussis toxin, carbachol both enhanced [Ca2+]i and stimulated somatostatin release. These data indicate that carbachol activates signals in D-cells that result in both increase and decrease in [Ca2+]i. The latter effect, which appears to be mediated via a pertussis toxin-sensitive guanine nucleotide binding protein, may be one mechanism responsible for cholinergic inhibition of somatostatin release.
Chiba
T
T
Third Department of Internal Medicine, Kobe University School of Medicine, Japan.
Fujita
T
T
Yamada
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D005748:Gastric Fundus / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010418:Pentagastrin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002217:Carbachol; D010418:Pentagastrin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium