CHARACTERIZATION OF β‐ADRENOCEPTORS IN MYOMETRIUM OF PREPARTURIENT RATS

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Abstract
Summary—The purpose of this study was to characterize the β‐adrenoceptor subtypes in pregnant rat myometrial membrane fractions and to determine the concentration of β2‐adrenoceptors in uterus during late pregnancy. Two methods are compared. A non‐subtype‐selective antagonist radioligand β‐[3H]dihydroalprenolol ([3H]DHA) was used to label all of the β‐adrenoceptors. [3H]DHA bound to both β1‐ and β2‐adrenoceptors with indistinguishable affinity (KD= 1.31 nM, Bmax= 174 fmol/mg protein). Computer modelling of competition curves of unlabeled selective antagonists or agonists was then required in order to determine reliably β1‐ and β2‐adrenoceptor affinities and proportions: the β2‐adrenoceptors represent 35.5% and the β2‐adrenoceptors 64.5% of the entire β‐adrenoceptor population in rat gravid myometrium at term.The second approach utilized the radioligand [3H]hydroxybenzylisoproterenol ([3H]HBI) which is a very high‐affinity β‐adrenoceptor agonist. The characteristics of the (3H)HBI binding sites are essentially those expected of β2‐adrenoceptors, but the [3H]HBI binding sites represent only 34% of [3H]DHA binding sites and may represent the fraction of β2‐adrenoceptors that mediate adenylate cyclase stimulation and uterine relaxation.Between 21 d 09 h and 22 d 09 h of gestation, the number of β2‐adrenoceptors was constant (mean = 225.6±20.2 fmol/mg protein). At term, the number of [3H]HBI binding sites dropped (‐75%) during the last 7 h of pregnancy, suggesting a reduced ability to elicit relaxation through β‐adrenoceptor activation in parturient myometrium of rat.