Effects of histamine H2 receptor antagonists on acid secretion stimulated by imidazoline derivatives in isolated parietal cells.

Both the effect of imidazoline derivatives on acid secretion and the mechanism of this effect were studied in the parietal cells isolated from guinea pigs. Clonidine and tolazoline both stimulated the parietal cells to elevate the concentration of cyclic AMP and the accumulation of [14C]aminopyrine concentration dependently, although these imidazoline derivatives are known as alpha 2-adrenoceptor agonist or antagonist. These stimulatory effects were inhibited by famotidine, ranitidine and cimetidine, histamine H2 receptor antagonists. However, [3H]clonidine binding to the membrane preparations of parietal cells was not affected by these H2 antagonists and yohimbine but was inhibited by imidazoline derivatives. These results suggest that imidazoline derivatives may bind to the specific binding sites (different from H2 receptor or alpha 2-adrenoceptor) and stimulate the acid secretion of parietal cells with an increase of cyclic AMP, and that H2 antagonists may not only compete with the agonists for receptor binding but also interfere with the receptor adenylate cyclase system.