Divergent stimulatory and inhibitory actions of carbamoylcholine on gastric D-cells.

Carbamoylcholine (carbachol) has been shown to inhibit somatostatin release from gastric D-cells. We observed that this dose-dependent inhibitory effect was accompanied by decreases in cellular cyclic adenosine 3':5'-monophosphate (cAMP) production and increases in parameters of membrane inositol phospholipid turnover. However, after pretreatment of D-cells with pertussis toxin (200 ng/ml), carbachol paradoxically stimulated basal somatostatin release and potentiated the secretagogue action of forskolin. Pertussis toxin pretreatment blocked the ability of carbachol to decrease cAMP production but changes in inositol phospholipid turnover were unaffected. Atropine reversed all of the observed changes induced by carbachol. These data suggest that muscarinic cholinergic receptors mediate both stimulatory and inhibitory regulation of D-cells. The inhibitory effect may involve pertussis toxin-sensitive inhibitory guanine nucleotide binding proteins while the stimulatory effect may result from the consequences of membrane phosphoinositide turnover.