title: Characterization of postjunctional alpha-adrenoceptors in the pithed mouse.
abstract: The adrenoceptor subtypes responsible for the pressor response to alpha1- and alpha2-adrenoceptor agonists have not yet been established, although gene knockout experiments in the mouse have provided evidence for a role of the alpha1B- and alpha2B-adrenoceptor. We have evaluated the blood pressure response to selective activation of postjunctional alpha1- and alpha2-adrenoceptors in the pithed mouse. The pressor response to phenylephrine was sensitive to blockade by terazosin, a selective alpha1-adrenoceptor antagonist, but insensitive to rauwolscine, an antagonist at alpha2-adrenoceptors. Phentolamine, a nonselective alpha-adrenoceptor antagonist, blocked the response to either phenylephrine or the selective alpha2-adrenoceptor agonist B-HT 933, whereas rauwolscine blocked only B-HT 933. A dose of terazosin effective against phenylephrine had no effect on B-HT 933; however, the B-HT 933 response was antagonized when the terazosin dose was increased tenfold. A high dose of doxazosin, an alpha1-adrenoceptor antagonist having no affinity for the alpha2B adrenoceptor, blocked the response to phenylephrine but not B-HT 933. Comparison of the potencies of these antagonists against the pressor response to phenylephrine with their affinities for recombinant alpha1-adrenoceptor subtypes suggests that this response is mediated by either alpha1B- or alpha1D-adrenoceptors. The alpha2B-adrenoceptor subtype is likely to take part in the response to B-HT 933. The ability of certain quinazoline alpha1-adrenoceptor antagonists to block the alpha2B adrenoceptor may contribute to their activity as antihypertensive agents.
authors.affiliation: SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: McCafferty
authors.forename: D P
authors.initials: DP
authors.lastname: Naselsky
authors.forename: J P
authors.initials: JP
authors.lastname: Hieble
mesh_terms: D016475:3T3 Cells; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009451:Neuroeffector Junction / Q000187:drug effects / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D011993:Recombinant Fusion Proteins; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D015016:Yohimbine; C041226:Terazosin; C015603:azepexole; D011224:Prazosin; D010646:Phentolamine