cAMP-independent mechanism is significantly involved in beta2-adrenoceptor-mediated tracheal relaxation.
The role of cAMP in the beta2-adrenoceptor-mediated relaxation in response to salbutamol was examined in guinea pig tracheal smooth muscle. The concentration-dependent salbutamol-induced relaxation was antagonized in a competitive fashion by a beta2-selective adrenoceptor antagonist, butoxamine, with a pA2 value of 6.90. Salbutamol (10 microM) elevated the tracheal smooth muscle cAMP content by about fivefold, a response which was significantly inhibited by an adenylyl cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536, 100 microM). However, the salbutamol-elicited relaxation was not diminished by SQ 22,536 (100 microM). These results provide evidence for the first time that a cAMP-independent mechanism(s) is involved in beta2-adrenoceptor-mediated tracheal smooth muscle relaxation in the guinea pig.
Koike
Katsuo
K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Miyama 2-2-1, Funabashi City, Chiba 274-8510, Japan.
Yamashita
Yoko
Y
Horinouchi
Takahiro
T
Yamaki
Fumiko
F
Tanaka
Yoshio
Y
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D002078:Butoxamine; C026777:ICI 118551; D000242:Cyclic AMP; D000420:Albuterol