Secretagogue stimulation of [14C]aminopyrine accumulation by isolated canine parietal cells

Abstract

Isolated canine gastric mucosal cells accumulate [14C]aminopyrine (AP) when treated with histamine, gastrin, and carbachol. In fractions of varying parietal cell content, this accumulation of AP correlated with the parietal cell content. Cimetidine caused parallel displacement of the dose-response curve to histamine, but failed to alter the response to carbachol or gastrin. Atropine caused parallel displacement of the dose-response curve to carbachol, but failed to inhibit the response to histamine or gastrin. The dissociation constants (Kb) for cimetidine inhibition of histamine and for atropine inhibition of carbachol were found to be 1.0 micro M and 1.3 nM, respectively, values comparable to those reported for other tissues. Thus, the isolated parietal cell appears to have pharmacologically typical H2- and muscarinic receptors, with gastrin acting at a third receptor site. Isobutyl methylxanthine (IMX) and the cAMP analogues dibutyryl cAMP (DBcAMP) and 8-bromo cAMP (but not the same analogues of cGMP) also stimulated AP accumulation. Atropine failed to inhibit the responses to IMX or DBcAMP, whereas cimetidine did inhibit the response to IMX, but not to DBcAMP.