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

Abstract

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 .mu.M), resulted in an enhanced histamine response in 8 of 8 parenchymal strips and in 4 of 8 tracheal spirals. On the average the parenchymal strips were 20 times more sensitive to histamine (P < 0.001); the tracheal spirals demonstrated an insignificant, 20%, increase in sensitivity after metiamide treatment. Apparently, there are inhibitory H2-receptors in guinea pig airways and they predominate in the periphery. When effects of H2-antagonism on the histamine response were determined in vivo, histamine response was enhanced only in animals treated with the .beta.-receptor antagonist propranolol. In these animals there was a mean 2.2-fold increase in histamine sensitivity. Although there are inhibitory H2-receptors in the guinea pig lung, their role in modulating the in vivo response is apparently much less than .beta.-adrenergic mechanisms.