title: Antagonistic effects of antimuscarinic drugs on alpha 1-adrenoceptors.
abstract: We previously observed that noradrenaline (NA)-induced contraction of the portal vein of rabbit was relaxed by the antimuscarinic drugs of atropine sulfate, but not scopolamine hydrobromide. In the present study we examined the possible effect of the antimuscarinic drugs of atropine sulfate, scopolamine hydrobromide, p-fluoro-hexa-hydro-sila-difenidol ( p-F-HHSiD, the M(3)-receptor antagonist) and pirenzepine (the M(1)-receptor antagonist) on alpha(1)-adrenoceptor (AR). Atropine and p-F-HHSiD relaxed the alpha(1)-AR agonist methoxamine-induced contraction of the rabbit portal vein in a concentration-dependent manner; however, scopolamine and pirenzepine had no such inhibitory effect. Radioligand binding studies with the alpha(1)-AR ligand 2-[2-(4-hydroxy-3-[(125)I]iodo-phenyl)ethylaminomethyl]-alpha-tetralone ([(125)I]HEAT) in membrane preparations from mouse whole brain showed that atropine (p K(i)=5.33) and p-F-HHSiD (p K(i)=5.88) had higher affinities than scopolamine (p K(i)=3.17) and pirenzepine (p K(i)<2.70). Furthermore, atropine and p-F-HHSiD had higher affinities for all human cloned alpha(1)-ARs than scopolamine and pirenzepine. The results show that the antimuscarinic drugs atropine and p-F-HHSiD have a direct but weak antagonistic activity against alpha(1)-ARs.
authors.affiliation: Department of Molecular, Cell Pharmacology, National Center for Child Health and Development Research Institute, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8509, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Shinoura
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Teranishi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tsuru
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D018340:Receptors, Adrenergic, alpha-1; C058297:4-fluorohexahydrosiladifenidol; D001285:Atropine