Inhibition of 14C-aminopyrine accumulation in isolated rabbit gastric glands by the H2-receptor antagonist HOE 760 (TZU-0460)

Acid secretion in isolated rabbit gastric glands was measured by means of the 14C-aminopyrine accumulation technique. Hoe 760 (TZU-0460) and Hoe 062, the desacetylated compound of Hoe 760, caused a concentration-dependent reduction of histamine (100 microM) induced aminopyrine-accumulation. The IC50-values were 3.16 +/- 0.84 microM (n = 5) and 1.58 +/- 0.6 microM (n = 6) for Hoe 760 and Hoe 062, respectively. In comparison an IC50 of 9.0 +/- 0.72 microM (n = 6) was obtained for cimetidine and 3.3 +/- 1.4 microM (n = 5) for ranitidine. The IC50-values of ranitidine, Hoe 760 and Hoe 062 were significantly different (p less than 0.05) from cimetidine. The addition of increasing concentrations of Hoe 760 to the histamine concentration-response curve caused a parallel rightward shift. The transformation of these concentration-response curves according to Arunlakshana and Schild indicated that this inhibition was caused by a competitive antagonism of the Histamine Receptor on the parietal cell. In agreement with these findings the dbc-AMP stimulated aminopyrine accumulation remained unaffected by the H2-receptor antagonists.