Subclasses of muscarinic receptors in isolated gastric mucosal cells: receptor characterization and parietal cell function.

Muscarinic receptors were characterized in isolated intact chief and parietal cell enriched cell populations from canine and guinea-pig gastric mucosa by binding of tritiated N-methylscopolamine ([3H]NMS). Antagonist and agonist binding was studied by displacement of [3H]NMS with non-radioactive atropine, pirenzepine, pilocarpine and carbachol. Model analysis points to the existence of two binding sites in each of the two cell populations. The number of binding sites per cell was 1.7-1.8 times higher in parietal than in chief cell populations. Subclasses of muscarinic receptors as characterized by pirenzepine binding were compatible with the suggested A- and C- (high and low affinity) binding sites. The observation that in canine cells GMPPNP induced a conformational change of the high affinity binding site for pirenzepine could suggest that their proportion might depend on environmental factors. Binding parameters were related to specific parietal cell function as measured by aminopyrine accumulation as index for acid secretion. The carbachol effects depended on the calcium concentration and were competitively inhibited by pirenzepine. The physiological relevance of muscarinic receptor heterogeneity in gastric mucosal cells is unknown although the data support the hypothesis that involvement of muscarinic binding sites in calcium transport mechanisms connected with parietal cell function and possible conformational changes of the binding sites might be regulatory parameters in gastric secretory processes.