Mechanisms for the stimulatory and inhibitory effects of carbamoylcholine on canine gastric D-cells.

We have previously reported that carbamoylcholine (carbachol), a recognized inhibitor of somatostatin release from D-cells, can act as stimulant following pretreatment of cells with pertussis toxin. In the present studies we have observed that pertussis toxin reverses the inhibitory effects of carbachol on D-cell stimulated with either cAMP or 12-O-tetradecanoyl-phorbol 13-acetate. Furthermore, the stimulatory effects of carbachol on D-cells pretreated with pertussis toxin potentiated the actions of pentagastrin without further enhancing the release of 3H-inositol triphosphate from prelabeled cells. These studies suggest that carbachol exerts its inhibitory effects on D-cells via pertussis toxin sensitive guanine nucleotide binding proteins at a point distal to the activation of different signal transduction mechanisms and that the stimulatory effects of carbachol are mediated by mechanisms that are independent of membrane phosphoinositide turnover.