Characterization of putative beta-adrenoceptors in the myometrium of the pregnant ewe: correlation between the binding of [3H] dihydroalprenolol and the inhibition of myometrial contractility in vitro

Publisher Website
Google Scholar
Abstract
.beta.-Adrenoceptors in the myometrium of the pregnant ewe were studied both functionally and by radioligand binding techniques using [3H] dihydroalprenolol (DHA). Spontaneous contractile activity in vitro was inhibited by .beta.-adrenoceptor agonists in a stereoselective manner: the order of potency suggested a .beta.2-adrenoceptor was involved. The effects of salbutamol were antagonized competitively by propranolol but the antagonism demonstrated by atenolol and ICI 118,551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropyl-aminobutan-2-ol] (.beta.1-and .beta.2-selective, respectively) was complex. DHA binding was saturable, rapidly reversible, stereoselective and appeared to occur to a single class of noninteracting sites with a Kd of 4.1 .+-. 0.3 nM and a maximal capacity of 0.8 .+-. 0.05 pmol/mg protein. Agonists demonstrated the same order of potency in competition for ligand binding sites as in inhibition of contractile activity. The DHA binding sites apparently were part of the .beta.-adrenoceptor. Strong agonists occupied only 0.1% of all receptors to produce the full response. Competition experiments with antagonists produced complex curves which could be resolved into 2 components comprising .apprx. 70 and 30% of the total number of sites. These sites apparently respresented .beta.2- and .beta.1-adrenoceptors, respectively. The possibility of regulation of the relative numbers of .beta.2- and .beta.1-adrenoceptors in the myometrium was discussed.