Dissociation constants and relative efficacies estimated from the functional antagonism of beta-adrenoceptor agonists on transmural stimulation in rat vas deferens.
In rat vas deferens, the beta-adrenoceptor agonists, isoprenaline, salbutamol, terbutaline and fenoterol, inhibited the contractions elicited by transmural electrical stimuli to an extent which depended on voltage magnitude. The dose-response curves for these agonists were shifted slightly to the right when the amplitude of the twitch was increased up to twice its original size. Consequently, the values of pD2 for the respective agonists obtained with a '50% twitch' and a '100% twitch' were: 7.6 and 7.5, 6.8 and 6.6, 6.2 and 6.0, 7.6 and 7.4. In addition, the maximal effects of the agonists were significantly reduced (by 13-18%). The values of other parameters for the same agonists, calculated according to a model for functional antagonism, were: negative log of dissociation constants (pKa): 7.2, 6.3, 6.2 and 7.2; percent receptors occupied to induce a half-maximal effect (y50): 42, 46, 63, and 53; relative intrinsic efficacy (er): 1.0, 0.9, 0.7, and 0.8. The usefulness of this type of functional antagonism as an alternative method for the estimation of drug-receptor parameters is discussed in the light of receptor theory.
Diaz-Toledo
A
A
Department of Pharmacology, Escola Paulista de Medicina, São Paulo, Brazil.
Jurkiewicz
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005280:Fenoterol / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D013726:Terbutaline / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D005280:Fenoterol; D007545:Isoproterenol; D013726:Terbutaline; D000420:Albuterol