ANGIOTENSIN-II RECEPTORS INDUCE TYROSINE DEPHOSPHORYLATION IN RAT FETAL MEMBRANES

Recently, it has become clear that many of the intracellular signals m ediated by Ang II receptors are similar to the signaling pathways acti vated by receptor tyrosine kinases. In the present paper, we are repor ting a full characterization of Ang II receptors in rat fetal membrane s. We assayed binding of the Ang II antagonist [I-125]Sar(1)Ile(8)Ang II and the AT(2) specific competitor [I-125]CGP42112. Both ligands exh ibited a rapid equilibrium and a high specificity for Ang II receptors . Competition studies confirmed the presence of both receptor subtypes , with a predominance of AT(2) receptors and the following order of po tency: CGP42112>Ang II > Losartan > PD123177. Immunoblotting studies o f tyrosine phosphoproteins showed that Ang II (10(-6) M) mediates a ra pid reduction in tyrosine phosphorylation of several proteins with app arent molecular masses in the range of 30-45 kDa. Increasing concentra tions of Ang II (10(-9)-10(-6) M) showed a dose-response behavior, sug gesting a clear physiological role of the observed effect. The respons e, blocked by Losartan and PD123177, seems to be mediated by both rece ptor subtypes. These results clearly indicate that both Ang II recepto rs mediate tyrosine dephosphorylation in early stages of development a nd support a role of these receptors in growth and development. (C) 19 98 Elsevier Science B.V.