Atypical beta-adrenoceptor- (beta 3-adrenoceptor) mediated relaxation of canine isolated bronchial smooth muscle.
To determine whether atypical beta-adrenoceptors (beta 3-adrenoceptors) exist in the airway smooth muscle, we studied isolated bronchial segments from dogs under isometric conditions in vitro. Addition of beta-adrenoceptor agonists produced a concentration-dependent relaxation of tissues precontracted with 10(-5) M acetylcholine, rank-order potency being isoproterenol (1) > or = salbutamol (0.95) > or = BRL 37344, a beta 3-selective adrenoceptor agonist (0.83) > norepinephrine (0.10). Under the condition that alpha- and beta 1-adrenoceptors had been blocked, the relaxant response to salbutamol was competitively antagonized by the beta 2-adrenoceptor antagonist ICI 118551 and the pA2 was 7.01 +/- 0.25 (SE), whereas the response to BRL 37344 was resistant, with an apparent pA2 of 5.66. However, cyanopindolol, an antagonist for atypical beta-adrenoceptors, antagonized the BRL-induced relaxation in a competitive manner, with a pA2 of 6.74 +/- 0.11. This pA2 was lower than that when salbutamol was used as an agonist (P < 0.05). Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were increased by BRL 37344 in a concentration-dependent fashion. These results suggest that beta 3-adrenoceptors may exist in canine bronchial smooth muscle and that the stimulation of this type of receptor causes a bronchodilation through a cAMP-dependent pathway.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Yamauchi
F
F
Chiyotani
A
A
Yamawaki
I
I
Takeuchi
S
S
Konno
K
K
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C047975:cyanopindolol; C057368:BRL 37344; D010869:Pindolol; C025716:ICI 89406; D000242:Cyclic AMP; D007545:Isoproterenol; D000109:Acetylcholine; D000420:Albuterol; D009638:Norepinephrine; D010646:Phentolamine