Atypical adrenoceptor-mediated relaxation of canine pulmonary artery through a cAMP-dependent pathway.
We studied the existence of beta 3-adrenoceptors in canine pulmonary artery smooth muscle under isometric conditions in vitro. A rank order potency of vascular relaxation was isoproterenol > salbutamol > selective beta 3-adrenoceptor agonists, CL 316243 and BRL 37344. A marked desensitization to salbutamol occurred by pretreatment with salbutamol but not with CL 316243. When beta 1-adrenoceptors were blocked, the relaxant responses to salbutamol were competitively antagonized by the beta 2-adrenoceptor antagonist ICI 118551, whereas the response to CL 316243 was not. Cyanopindolol, a non-selective beta-adrenoceptor antagonist, antagonized CL 316243-induced relaxation in a competitive manner with a pA2 of 6.10, and this value was lower than that when salbutamol was used as an agonist (6.69). Intracellular cAMP levels were increased by CL 316243, an effect that was not altered by ICI 118551. Therefore, beta 3-adrenoceptors may be present and functioning in canine pulmonary artery.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tagaya
E
E
Isono
K
K
Nagai
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004149:Dioxoles / Q000494:pharmacology; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004149:Dioxoles; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C026777:ICI 118551; C047975:cyanopindolol; C057368:BRL 37344; D010869:Pindolol; D000242:Cyclic AMP; D007545:Isoproterenol; D000420:Albuterol