Alteration of histamine response by H2-receptor antagonism in the guinea pig.

Effects of H2-receptor antagonism on the response to histamine was studied in the guinea pig in vivo and in vitro. The H2-receptor antagonist, metiamide (100 micro M), resulted in an enhanced histamine response in eight of eight parenchymal strips and in four of eight tracheal spirals. On the average the parenchymal strips were 20-fold more sensitive to histamine (P less than 0.001), whereas the tracheal spirals demonstrated an insignificant, 20%, increase in sensitivity after metiamide treatment. These results are consistent with the hypothesis that there are inhibitory H2-receptors in guinea pig airways and they predominate in the periphery. When we determined the effects of H2-antagonism on the histamine response in vivo we found that the histamine response was enhanced only in animals that had been treated with the beta-receptor antagonist propranolol. In these animals there was a mean 2.2-fold increase in histamine sensitivity. These results suggest that although there are inhibitory H2-receptors in the guinea pig lung, their role in modulating the in vivo response is much less than beta-adrenergic mechanisms.