Dissociation constants and relative efficacies estimated from the functional antagonism of beta-adrenoceptor agonists on transmural stimulation in rat vas deferens

European Journal of Pharmacology
A Díaz-Toledo, A Jurkiewicz

Abstract

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.

References

Dec 1, 1985·Naunyn-Schmiedeberg's Archives of Pharmacology·J M MayK P Minneman
Mar 1, 1970·The Bulletin of Mathematical Biophysics·R J TallaridaC Harakal
Dec 5, 1980·European Journal of Pharmacology·V J LottiP Kling
May 1, 1981·British Journal of Pharmacology·D MacKay
May 1, 1981·British Journal of Pharmacology·J Emmerson, D MacKay
Sep 29, 1956·Nature·M NICKERSON

Citations

Jul 4, 1996·European Journal of Pharmacology·N H JurkiewiczA Jurkiewicz
Mar 10, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Xinfeng ZhaoWeijin Zang

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