Comparison of the alpha-adrenoceptor-mediated effects of beta3-adrenoceptor ligands in rat pulmonary artery.
We have recently shown that the beta-adrenoceptor ligands CGP 12177, bupranolol, and SR 59230A (aryloxypropanolamines), but not BRL 37344 and CL 316243 (phenylethanolamines), exhibit significant affinity for alpha1-adrenoceptors and that CGP 12177 displays partial agonist properties at alpha-adrenoceptors in rat pulmonary artery. In this study, bupranolol and SR 59230A were further evaluated for their potential alpha-adrenoceptor mediated effects (i.e., agonist and/or antagonist properties) in rat intralobar pulmonary artery and compared with BRL 37344 and CL 316243. Bupranolol induced a relaxation in phenylephrine-precontracted arteries, but had no effect in prostaglandin F2alpha(PGF2alpha) -precontracted ones. SR 59230A also elicited a relaxation in phenylephrine-precontracted arteries. In PGF2alpha -precontracted arteries, SR 59230A induced a contractile response that was insensitive to the irreversible alpha-adrenoceptor antagonist phenoxybenzamine. BRL 37344 at high concentrations, but not CL 316243, produced slight relaxation in both phenylephrine- and PGF2alpha -precontracted arteries. The contractile response to phenylephrine was antagonized by bupranolol and SR 59230A in a competitive manner (pA2: 6.38 and 7.08 respectively). The concentration-response curve to phenylephrine was also shifted to the right by BRL 37344 (mean pKb: 4.45), but not by CL 316243 (100 microM). This study indicates that the aryloxypropanolamine derivatives bupranolol and SR 59230A exhibit competitive antagonist, but no agonist properties on alpha1-adrenoceptors, SR 59230A also inducing alpha-adrenoceptor-independent contraction. Among the phenylethanolamines, BRL 37344 but not CL 316243, also exerts an antagonist effect on alpha1-adrenoceptors, with a much lower potency than the aryloxypropanolamines studied.
Leblais
Véronique
V
Laboratoire de Pharmacologie de la Faculté de Pharmacie, Université Victor Segalen Bordeaux 2, Casier 83 Inserm, E356 146 rue Léo Saignat, Bordeaux cedex 33076, France. veronique.leblais@phcodyn.u-bordeaux2.fr
Pourageaud
Fabrice
F
Ivorra
M Dolores
MD
Marthan
Roger
R
Muller
Bernard
B
D058668:Adrenergic alpha-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002046:Bupranolol / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058668:Adrenergic alpha-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004149:Dioxoles; D004983:Ethanolamines; D008024:Ligands; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C057368:BRL 37344; D002046:Bupranolol