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.
Sakuta
H
H
Department of Pharmacology, National Defense Medical College, Saitama, Japan.
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D006080:Ovarian Follicle; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D014982:Xenopus laevis
D001578:Benzopyrans; D006634:Histamine H1 Antagonists; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; C074338:Y 26763; D011188:Potassium; D005905:Glyburide