Ca2+ inhibition of type III adenylyl cyclase in vivo

Gary A. Wayman, Soren Impey, Daniel R. Storm

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Type III adenylyl cyclase is stimulated by β-adrenergic agonists and glucagon in vitro and in vivo, but not by Ca2+ and calmodulin. However, the enzyme is stimulated by Ca2+ and calmodulin in vitro when it is concomitantly activated by the guanyl nucleotide stimulatory protein Gs (Choi, E. J., Xia, Z., and Storm, D. R. (1992a) Biochemistry 31, 6492-6498). Here, we examined regulation of type III adenylyl cyclase by Gs-coupled receptors and intracellular Ca2+ in vivo. Surprisingly, intracellular Ca2+ inhibited hormone-stimulated type III adenylyl cyclase activity. Submicromolar concentrations of intracellular free Ca2+, which stimulated type I adenylyl cyclase, inhibited glucagon- or isoproterenol-stimulated type III adenylyl cyclase. Inhibition of type III adenylyl cyclase by intracellular Ca2+ was not mediated by Gi, cAMP-dependent protein kinase, or protein kinase C. However, an inhibitor of CaM kinases antagonized Ca2+ inhibition of the enzyme, and coexpression of constitutively activated CaM kinase II completely inhibited isoproterenol-stimulated type III adenylyl cyclase activity. We propose that Ca2+ inhibition of type III adenylyl cyclase may serve as a regulatory mechanism to attenuate hormone-stimulated cAMP levels in some tissues.

Original languageEnglish (US)
Pages (from-to)21480-21486
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number37
StatePublished - Sep 15 1995
Externally publishedYes

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Calmodulin
Glucagon
Isoproterenol
Hormones
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Adrenergic Agonists
Biochemistry
Enzymes
Cyclic AMP-Dependent Protein Kinases
adenylate cyclase 3
Protein Kinase C
Phosphotransferases
Nucleotides
Tissue
Proteins
In Vitro Techniques
adenylyl cyclase 1

ASJC Scopus subject areas

  • Biochemistry

Cite this

Wayman, G. A., Impey, S., & Storm, D. R. (1995). Ca2+ inhibition of type III adenylyl cyclase in vivo. Journal of Biological Chemistry, 270(37), 21480-21486.

Ca2+ inhibition of type III adenylyl cyclase in vivo. / Wayman, Gary A.; Impey, Soren; Storm, Daniel R.

In: Journal of Biological Chemistry, Vol. 270, No. 37, 15.09.1995, p. 21480-21486.

Research output: Contribution to journalArticle

Wayman, GA, Impey, S & Storm, DR 1995, 'Ca2+ inhibition of type III adenylyl cyclase in vivo', Journal of Biological Chemistry, vol. 270, no. 37, pp. 21480-21486.
Wayman, Gary A. ; Impey, Soren ; Storm, Daniel R. / Ca2+ inhibition of type III adenylyl cyclase in vivo. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 37. pp. 21480-21486.
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