Inhibition by histamine H1 receptor antagonists of endogenous glibenclamide-sensitive K+ channels in follicle-enclosed Xenopus oocytes.

Effects of histamine receptor ligands on the glibenclamide-sensitive K+ currents induced by K+ channel openers, cromakalim and Y-26763, were examined in follicle-enclosed Xenopus oocytes. Histamine H1 receptor antagonists, promethazine, dimethindene and chlorpheniramine all decreased cromakalim-induced K+ currents with IC50 values of 31.5 microM, 29.5 microM and 138 microM, respectively. These compounds also blocked Y-26763-induced K+ currents with comparable IC50 values. Histamine (1 mM) and histamine H2 receptor antagonists, cimetidine (0.5 mM) and ranitidine (1 mM) had little effect on these K+ currents. These results suggest that histamine H1 receptor antagonists inhibit glibenclamide-sensitive K+ currents by a mechanism other than the histamine H1 receptor antagonism. The inhibitory effects might explain, in part, the reported actions of histamine H1 receptor antagonists in ischemia.