alpha2B-adrenoceptor agonist ST-91 antagonizes beta2-adrenoceptor-mediated relaxation in rat mesenteric artery rings.
We sought an isolated vascular preparation and experimental setting where the function of alpha2B-adrenoceptors could be demonstrated by non-recombinant technique. ST-91 (2-[2,6-diethylphenylamino]-2-imidazoline), an alpha 2B-adrenoceptor agonist with a mixed alpha adrenergic receptor type/subtype selection profile antagonized the relaxant effect of isoproterenol in endothelium-denuded rat mesenteric artery rings precontracted with phenylephrine. At 10(-7) M of ST-91, the antagonism was characterized by a rightward shift of isoproterenol dose-response curve (A50=6.81+/-1.40 e-7 (n=4) vs the control 1.29+/-0.25 e-7 M (n=4)) with no E(max) depression. At 10(-6) M the Emax depression was prevalent (36.1+/-7.0% (n=4) vs the control 79.9+/-5.1% (n=4)); both actions could be antagonized by the alpha2-adrenoceptor antagonist yohimbine. The not subtype-selective alpha(2)-adrenoceptor agonist xylazine (10(-7) M) did not affect the relaxant action of isoproterenol. Present findings are discussed in the light of previously reported hemodynamic effects attributed to alpha2B-adrenoceptors in receptor subtype-knockout animals.
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Medical Faculty, Budapest, Hungary.
Erzsébet
E
Kató
Lóránt
L
Lipták
Nashwan
N
Shujaa
Péter
P
Mátyus
Klára
K
Gyires
András Z
AZ
Rónai
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D013726:Terbutaline / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014991:Xylazine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
C547770:Adra2a protein, rat; C547773:Adra2b protein, rat; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; D010656:Phenylephrine; D014991:Xylazine; D015016:Yohimbine; C011266:ST 91; D007545:Isoproterenol; D003000:Clonidine; D013726:Terbutaline; D011224:Prazosin