Evidence for participation of calcineurin in potentiation of agonist-stimulated cyclic AMP formation by the calcium-mobilizing hormone, angiotensin II.

摘要: Angiotensin II (AII) receptors are known to interact with two distinct guanine nucleotide binding proteins, Gq/11 and Gi, in rat adrenal glomerulosa cells activate phospholipase C inhibit adenylate cyclase, respectively. However, cultured bovine AII potentiates rather than inhibits the stimulatory effect of adrenocorticotropin (ACTH) on cAMP levels. This was partially mimicked by phorbol 12-myristate 13-acetate (PMA) inhibited staurosporine or depletion protein kinase but unaffected pertussis toxin treatment. No potentiation detectable disrupted membrane preparations. In intact cells, treatment cyclosporin A FK506 completely AII- PMA-induced production without affecting response ACTH. COS-7 transfected AT1 receptor, caused 2-3-fold enhancement ACTH-induced response, an that reproduced PMA. These potentiating actions PMA were prevented preincubation FK506, latter abolished rapamycin. results implicate Ca2+- calmodulin-dependent phosphatase, calcineurin, AII-induced cyclase activity both cells. The finding enhances ACTH-stimulated a second messenger-mediated mechanism involves participation calcineurin reveals additional mode cross-talk between pathways activated Ca(2+)-mobilizing cAMP-generating receptors.