Possible mechanisms of beta-adrenoceptor-mediated relaxation induced by noradrenaline in guinea pig taenia caecum.
The mechanisms of the beta-adrenoceptor-mediated relaxation induced by noradrenaline in guinea pig taenia caecum were investigated. Noradrenaline caused graded relaxation of this preparation. However, the concentration-response curves for noradrenaline were unaffected by propranolol (approximately 10(-5) M) or phentolamine (approximately 10(-5) M). The responses to noradrenaline were antagonized in a concentration-dependent manner by bupranolol, and Schild plots of the data revealed a pA2 value of 5.53. Also, bupranolol antagonized responses to isoprenaline, and Schild plots of the data revealed the pA2 value to be 8.53. Noradrenaline significantly increased the cyclic AMP level in this preparation. Bupranolol (10(-4) M) significantly decreased the cyclic AMP response elicited by noradrenaline, whereas propranolol (10(-5) M) produced no effect. These results suggest that the relaxant response to noradrenaline in guinea pig taenia caecum is mainly mediated by beta 3-adrenoceptors (or atypical beta-adrenoceptors) and that in guinea pig taenia caecum noradrenaline behaves as a beta 3-selective adrenoceptor agonist.
Koike
K
K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Horinouchi
T
T
Takayanagi
I
I
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002046:Bupranolol / Q000494:pharmacology; D002432:Cecum / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D009124:Muscle Proteins; D011943:Receptors, Adrenergic, beta; D002046:Bupranolol; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine