Biochemical studies of the beta-adrenoceptor of rat myometrium

• Main Author: Richardson, Andrew
• Published: University of Leicester 1979
• Subjects: 612.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.470407

The role of the beta-adrenoceptor in the hormonally controlled alterations in catecholamine responsiveness in the rat myometrium has been studied using biochemical techniques. After treatment with oestrogen or progesterone catecholamine agonists relaxed the rat myometrium. The response was greater in progesterone- than oestrogen-treated uteri, and was inhibited by propranolol. Catecholamine stimulated formation of uterine cyclic AMP in vivo and in myometrial slices was similar after either hormone treatment. The relative potencies of the catecholamine agonists was consistent with cyclic AMP formation being through a beta-adrenoceptor. Phosphodiesterase activity was the same after oestrogen or progesterone treatment. These results suggest that beta-adrenoceptor coupled cyclic AMP systems do not play a major role in the hormonal control of uterine contractile activity. Radiolabelled ligand binding studies were used to examine the beta-adrenoceptor directly. Using bovine lung as a source of beta-adrenoceptors, a study of the influence of the non-receptor binding of 3H-dihydroalprenolol on the subsequent analysis of the receptor binding was made. A theoretical consideration of this problem confirmed the experimental results that incorrect determination of non-receptor binding can introduce errors in the analysis of the specific receptor binding. The methods of analysing multiple receptor binding was examined and a computer program developed to aid analysis of data from these experiments. 3H-Dihydroalprenolol was used to directly examine the myometrial beta-adrenoceptor. 3H-Dihydroalprenolol bound to a site that had characteristics of the myometrial beta-adrenoceptor. The pharmacological specificity of a number of adrenoceptor agonists and antagonists showed interaction was at a beta2-adrenoceptor. After oestrogen treatment a small proportion of the 3-adrenoceptor population had characteristics of the 31-adrenoceptor, and suggests that a heterogeneous beta-adrenoceptor population is present under the influence of this hormone. The results are discussed in relation to both uterine and receptor pharmacology.