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.
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 (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. These data suggested that the DHA binding sites 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 two components comprising approximately 70% and 30% of the total number of sites. It was suggested that these sites represented 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.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000526:Alprenolol / Q000031:analogs & derivatives*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009215:Myometrium / Q000187:drug effects*; D011247:Pregnancy; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012756:Sheep; D014590:Uterine Contraction / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D001262:Atenolol; D004082:Dihydroalprenolol; D000526:Alprenolol; D011433:Propranolol; D000420:Albuterol