title: Investigation of alpha 1-adrenoceptor subtypes in canine aorta, using alkylating agents.
abstract: The ability of putative selective irreversible ligands SZL-49 (1-(4-amino-6,7-dimethoxy-2,5-diene-2-carbonyl)) and CEC (chlorethylclonidine), for alpha 1A and alpha 1B adrenoceptor subtypes, respectively, to affect alpha 1-adrenoceptors of canine aorta microsomal membranes was investigated. These membranes contain an apparently homogeneous population of [3H]prazosin binding sites. SZL-49, like phenoxybenzamine, abolished all binding of [3H]prazosin. CEC abolished 75% of the prazosin binding sites under the most stringent conditions we applied. However, the remaining 25% of binding sites was identical in affinity for prazosin with control membranes, and competition studies of other subtype-selective ligands revealed unchanged ability to complete against CEC-sensitive and -insensitive sites. We concluded that SZL-49 and CEC are not alpha 1A- and alpha 1B-adrenoceptor selective under in vitro conditions. Our data led to the hypothesis that canine aortic membranes contain exclusively alpha 1B-adrenoceptors but that current tools for identifying alpha 1-adrenoceptor subtypes proved inadequate in vitro in this study.
authors.affiliation: Department of Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: K H
authors.initials: KH
authors.lastname: Hoo
authors.forename: C Y
authors.initials: CY
authors.lastname: Kwan
authors.forename: E E
authors.initials: EE
authors.lastname: Daniel
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010109:Oxymetazoline / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000477:Alkylating Agents; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; C051307:SZL 49; C051731:chlorethylclonidine; D010109:Oxymetazoline; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D011224:Prazosin