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  • Title: Heterogeneity of alpha-2 adrenoceptors in pregnant rat uterus: identification of subtypes and autoradiographic distribution.
    Author: Legrand C, Mhaouty S, Rigolot C, Maltier JP.
    Journal: J Pharmacol Exp Ther; 1993 Jul; 266(1):439-49. PubMed ID: 8101224.
    Abstract:
    Pharmacological characterization of alpha-2 adrenoceptors of the pregnant rat myometrium was assessed using the ability of various alpha adrenoceptor agonists and antagonists to inhibit [3H]rauwolscine or [3H]idazoxan binding to myometrial 50,000 x g fraction or to slide-mounted sections of the whole pregnant uterus. Saturation binding studies with both radioligands showed that the number of myometrial alpha-2 adrenoceptors is greatly increased on days 10 to 12 of pregnancy vs. cyclic rats. It then decreased from midpregnancy to term (about -75%; P < .01) with no change of the equilibrium dissociation constant (between 7-11 nM). Chemical sympathectomy by 6-hydroxydopamine significantly decreased (P < .01) the density of alpha-2 adrenoceptors at days 8 and 12 of pregnancy. Later, 6-hydroxydopamine administration did not alter Bmax or Kd values suggesting that the pregnancy decrease of alpha-2 adrenoceptors may be related to a loss of presynaptic receptors. In order to identify myometrial postsynaptic alpha-2 adrenoceptor subtypes, the inhibition of [3H]rauwolscine or [3H]idazoxan binding by oxymetazoline, prazosin and chlorpromazine was studied on days 20 and 21 of pregnancy. All inhibition curves were consistent with a model of two classes of binding sites: about 55% of the myometrial alpha-2 adrenoceptors, which had a higher affinity for oxymetazoline, may represent the alpha-2A subtype whereas the other 45% of the sites, which had a higher affinity for prazosin and chlorpromazine, may represent the alpha-2B subtype. Autoradiographic studies using [3H]rauwolscine revealed that both subtypes are colocalized in the longitudinal muscle. A high density of alpha-2A and alpha-2B subtypes was also detected in the chorioallantoic and yolk sac placenta and in the embryonic nervous system.
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