Involvement of tyrosine phosphorylation and MAPK activation in the mechanism of action of ACTH, angiotensin II and vasopressin

ACTH, Angiotensin II (Ang II) and Vasopressin (AVP) are among the well known regulators of aldosterone secretion and also have a trophic action on the adrenal gland. According to classic studies, Ang II and AVP activate phospholipase C (PLC), diacylglycerol (DAG) and inositol phosphate (InsPs) production whereas ACTH activates cAMP production. However, our data indicate that the three peptides are able to induce a time-dependent increase in the level of Tyr-phosphorylation of several proteins. Western Blot analysis indicates a biphasic activation of Tyr-phosphorylation by AVP, with a peak at 30 s and a second one at 15 min incubation. Ang II induced a rapid (2 min) and sustained activation of Tyr-phosphorylation, while ACTH induced a progressive time course with a plateau reached at 15 min. Ang II and AVP also increased phosphorylation of p42(mapk) and p44(mapk), while ACTH did not affect MAPK activity. Moreover, pre-incubation of the cells with genistein (Tyr-kinase inhibitor) and PD 098059 (a MAPK inhibitor) did not affect InsPs production or aldosterone secretion induced by Ang II or AVP. These results suggest that the MAPK pathway is involved in the control of cell growth rather than aldosterone secretion.