Localization and characterization of alpha-2 adrenoceptors in the isolated canine pulmonary vein.
Alpha-1 and alpha-2 adrenoceptor-mediated contractile responses were studied in isolated canine pulmonary veins. Norepinephrine elicited concentration-dependent contractile responses which were antagonized in a competitive manner by the selective alpha-2 adrenergic antagonist, rauwolscine, with a dissociation constant of 15.7 nM, whereas the selective alpha-1 adrenoceptor antagonist, prazosin, produced nonparallel rightward shifts in the norepinephrine concentration-response curve with a marked depression in the maximal response, indicating noncompetitive antagonism. B-HT 933, a selective alpha-2 adrenoceptor agonist, also produced a concentration-dependent contraction in canine pulmonary vein, with the maximal contraction elicited by B-HT 933 being approximately 45% of that produced by norepinephrine. The response mediated by B-HT 933 was antagonized in a competitive manner by rauwolscine with a dissociation constant of 4.4 nM, whereas prazosin again behaved in a noncompetitive manner producing nonparallel rightward shifts in the B-HT 933 concentration-response curve with a marked depression in the maximal response. However, another alpha-1 adrenoceptor antagonist, corynanthine, weakly blocked the response produced by B-HT 933 with a dissociation constant of 1400 nM, and this low affinity for corynanthine is consistent with interaction at alpha-2 adrenoceptors. Cirazoline, a selective alpha-1 adrenoceptor agonist, also produced a concentration-dependent vasoconstrictor response in canine pulmonary veins which was antagonized competitively by both alpha-1 adrenoceptor antagonists, corynanthine and prazosin, with dissociation constants of 180 and 1.4 nM, respectively, indicative of an interaction with alpha-1 adrenoceptors. Rauwolscine (10 nM) did not significantly affect the response produced by cirazoline.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohlstein
E H
EH
Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pennsylvania.
Horohonich
S
S
Shebuski
R J
RJ
Ruffolo
R R
RR
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D010643:Phenoxybenzamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011667:Pulmonary Veins / Q000032:analysis / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D015016:Yohimbine; C015603:azepexole; D011224:Prazosin