Ca2+ inhibition of type III adenylyl cyclase in vivo

G A Wayman; S Impey; D R Storm

doi:10.1074/jbc.270.37.21480

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Ca2+ inhibition of type III adenylyl cyclase in vivo

Journal article

Open access

Peer reviewed

Ca2+ inhibition of type III adenylyl cyclase in vivo

G A Wayman, S Impey and D R Storm

The Journal of biological chemistry, Vol.270(37), pp.21480-21486

09/15/1995

DOI: https://doi.org/10.1074/jbc.270.37.21480

Handle:

https://hdl.handle.net/2376/113836

PMID: 7665559

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Abstract

Calcium - metabolism

Embryo, Mammalian

Humans

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives

Brain - enzymology

Recombinant Proteins - biosynthesis

Kidney

Adenylyl Cyclase Inhibitors

Isoquinolines - pharmacology

Transfection

Cattle

Isoenzymes - metabolism

Recombinant Proteins - metabolism

Cell Line

Recombinant Proteins - antagonists & inhibitors

Calcium - pharmacology

Gene Library

Guanylyl Imidodiphosphate - pharmacology

Adenylyl Cyclases - metabolism

Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors

Glucagon - pharmacology

Piperazines - pharmacology

Cell Membrane - enzymology

Animals

Receptors, Glucagon - biosynthesis

Isoproterenol - pharmacology

Kinetics

Isoenzymes - antagonists & inhibitors

Receptors, Glucagon - physiology

GTP-Binding Proteins - metabolism

Type III adenylyl cyclase is stimulated by beta-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.

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Title: Ca2+ inhibition of type III adenylyl cyclase in vivo
Creators: G A Wayman - Department of Pharmacology, University of Washington, Seattle 98195, USA
S Impey
D R Storm
Publication Details: The Journal of biological chemistry, Vol.270(37), pp.21480-21486
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: HL 44948 / NHLBI NIH HHS
Identifiers: 99900547653801842
Language: English
Resource Type: Journal article