Heterogeneity of alpha-2 adrenoceptors in pregnant rat uterus: identification of subtypes and autoradiographic distribution.
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.
Legrand
C
C
Laboratoire de Physiologie de la Reproduction, CNRS URA 1449, Université Pierre et Marie Curie, Paris, France.
Mhaouty
S
S
Rigolot
C
C
Maltier
J P
JP
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D019329:Idazoxan; D007700:Kinetics; D008853:Microscopy; D009215:Myometrium / Q000378:metabolism / Q000648:ultrastructure*; D016627:Oxidopamine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000032:analysis* / Q000145:classification* / Q000378:metabolism; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D015016:Yohimbine; D016627:Oxidopamine; D019329:Idazoxan