title: Characterization of histamine receptors in isolated pig basilar artery by functional and radioligand binding studies.
abstract: Histamine receptors in pig basilar arteries were investigated in vitro by radioligand binding assays and by measuring the contractile and relaxant responses to histamine. Histamine and 2-pyridylethylamine (H1-agonist) induced concentration-dependent contractions, whereas impromidine (H2-agonist) induced concentration-dependent relaxations. These responses were independent of the presence of endothelial cells. Diphenhydramine (H1-antagonist) partially reversed the histamine-induced contractions to relaxations. Cimetidine (H2-antagonist) potentiated the contraction in a concentration-dependent manner. In the presence of cimetidine, the pEC50 value of histamine for the contraction was 6.30, and diphenhydramine competitively antagonized the histamine-induced contractions (pA2, 7.77). In the presence of diphenhydramine, the pEC50 value of histamine for the relaxation was 5.93, and cimetidine competitively antagonized the histamine-induced relaxations (pA2, 6.62). In the binding studies, the Kd value of [3H]mepyramine was 2.1 nM and the Bmax value was 95.6 fmol/mg protein. A competition experiment with diphenhydramine showed that the pKi value (7.51) was similar to the pA2 value. The Kd value for [3H]cimetidine was 126.0 nM and the Bmax value was 459.8 fmol/mg protein. The pKd (6.90) for [3H]cimetidine was similar to the pA2 for cimetidine. The Hill coefficients for these experiments were not significantly different from unity. The present findings indicate that the number of H1-receptors, in terms of the Bmax value for [3H]mepyramine, is smaller than that of H2-receptors, in terms of the Bmax value for [3H]cimetidine. However, the contractile response to histamine is predominantly mediated through stimulation of H1-receptors on vascular smooth muscle cells in pig basilar artery.
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Miyamoto
authors.forename: A
authors.initials: A
authors.lastname: Nishio
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D002927:Cimetidine / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D011738:Pyrilamine / Q000378:metabolism; D011869:Radioligand Assay; D011969:Receptors, Histamine H1 / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine