Angiotensin II receptors induce tyrosine dephosphorylation in rat fetal membranes.
Recently, it has become clear that many of the intracellular signals mediated by Ang II receptors are similar to the signaling pathways activated by receptor tyrosine kinases. In the present paper, we are reporting a full characterization of Ang II receptors in rat fetal membranes. We assayed binding of the Ang II antagonist [125I]Sar1Ile8Ang II and the AT2 specific competitor [(125)1]CGP42112. Both ligands exhibited a rapid equilibrium and a high specificity for Ang II receptors. Competition studies confirmed the presence of both receptor subtypes, with a predominance of AT2 receptors and the following order of potency: CGP42112>Ang II>Losartan>PD123177. Immunoblotting studies of tyrosine phosphoproteins showed that Ang II (10(-6)M) mediates a rapid reduction in tyrosine phosphorylation of several proteins with apparent molecular masses in the range of 30-45 kDa. Increasing concentrations of Ang II (10(-9) - 10(-6)M) showed a dose-response behavior, suggesting a clear physiological role of the observed effect. The response, blocked by Losartan and PD123177, seems to be mediated by both receptor subtypes. These results clearly indicate that both Ang II receptors mediate tyrosine dephosphorylation in early stages of development and support a role of these receptors in growth and development.
Cátedra de Bioquímica Avanzada, Facultad de Química y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, Argentina. gciuffo@unsl.edu.ar
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Ciuffo
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Alvarez
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Fuentes
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001667:Binding, Competitive; D005260:Female; D007457:Iodine Radioisotopes; D007700:Kinetics; D010766:Phosphorylation; D051381:Rats; D011921:Rats, Inbred WKY; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007457:Iodine Radioisotopes; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C099368:angiotensin II, iodo-(Sar(1)-Ile(8))-; D014443:Tyrosine; D015059:1-Sarcosine-8-Isoleucine Angiotensin II