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

A. J. Baukal, L. Hunyady, K. J. Catt, T. Balla

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Abstract

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

Original languageEnglish
Pages (from-to)24546-24549
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number40
Publication statusPublished - Oct 19 1994

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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