Atypical adrenoceptor-mediated relaxation of canine pulmonary artery through a cyclic adenosine monophosphate-dependent pathway.
To determine whether functional atypical beta-adrenoceptors (beta(3)-adrenoceptors) are present in pulmonary vascular smooth muscle, we studied isolated canine pulmonary arterial rings under isometric conditions in vitro. Addition of beta-adrenoceptor agonists produced a concentration-dependent relaxation of noradrenaline-precontracted tissues, a rank order potency being isoproterenol (1) > salbutamol (0.95) > selective beta(3)-adrenoceptor agonists, CL 316243 (0.85), and BRL 37344 (0. 83). A marked desensitization to salbutamol occurred by pretreatment with salbutamol but not with CL 316243. When beta(1)-adrenoceptors had been blocked, the relaxant responses to salbutamol were competitively antagonized by the beta(2)-adrenoceptor antagonist ICI 118551 with a pA(2) value of 7.67 +/- 0.21 (mean +/- S.E.), but the response to CL 316243 was weekly antagonized by ICI 118551 only at a high concentration of 10(-5) M, where an apparent pA(2) value was 5. 24. In contrast, cyanopindolol, a nonselective beta-adrenoceptor antagonist, antagonized CL 316243-induced relaxation in a competitive manner with a pA(2) of 6.10 +/- 0.11. This pA(2) value was lower than that when salbutamol was used as an agonist (6.69 +/- 0.14, p < 0.01). Intracellular 3',5'-cyclic adenosine monophosphate (cAMP) levels were increased by CL 316243 in a concentration-dependent fashion, an effect that was not altered by ICI 118551. These results suggest that beta(3)-adrenoceptors may exist in canine pulmonary artery smooth muscle and that stimulation of this atypical receptor causes vasodilation through a cAMP-dependent pathway.
Tagaya
E
E
First Department of Medicine, Tokyo Women's Medical College, Tokyo 162, Japan.
Tamaoki
J
J
Takemura
H
H
Isono
K
K
Nagai
A
A
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D004285:Dogs; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011651:Pulmonary Artery / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D014664:Vasodilation / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D000242:Cyclic AMP