ACTION OF β‐ADRENOCEPTOR ANTAGONISTS ON THE RESPONSE TO ISOPRENALINE IN THE OESTROGEN DOMINATED RABBIT UTERUS

Abstract

1 Log dose-response curves to isoprenaline from spontaneously contracting muscle strips from rabbit uterus have been obtained. The effects of the α-adrenoceptor antagonists phentolamine and phenoxybenzamine, the β-adrenoceptor antagonists propranolol and practolol, and (+)-propranolol on the log dose-response curves were studied. 2 Phentolamine 5.3 × 10⁻⁷ M had a stimulating effect on the muscle strips, moving the log dose-response curve of isoprenaline to the right. Phenoxybenzamine 2.9 × 10⁻⁵ M had no effect on the curves. 3 Propranolol 3.4 × 10⁻⁶ M had no effect on the curves from circular muscle strips, with either phentolamine 5.3 × 10⁻⁷ M or with phenoxybenzamine 2.9 × 10⁻⁵ M as α-blocker. The curves from the longitudinal muscle strips were shifted somewhat to the right, the same shift, however, being obtained with (+)-propranolol 3.4 × 10⁻⁶ M. 4 Practolol 3.8 × 10⁻⁶, 3.8 × 10⁻⁵ and 3.8 × 10⁻⁴ M was without effect on the curves, either in the circular or in the longitudinal strips. 5 It is concluded that neither propranolol at 3.4 × 10⁻⁶ M nor practolol act as β-adrenoceptor antagonists in oestrogen dominated rabbit uterus. In all other tissues investigated, propranolol or practolol block the effect of isoprenaline. Whether the effect of isoprenaline in this tissue may be termed a β-effect, is then a question of definition. In addition there is no evidence for any extraneuronal uptake mechanisms for isoprenaline. 6 Variations in sensitivity to β-stimulation with the time of the year were observed, the sensitivity being greatest in the winter and lowest in the summer.