Abstract
Agonist-evoked [Ca2+]i oscillations have been considered a biophysical phenomenon reflecting the regulation of the IP3 receptor by [Ca2+]i. Here we show that [Ca2+]i oscillations are a biochemical phenomenon emanating from regulation of Ca2+ signaling by the regulators of G protein signaling (RGS) proteins. [Ca2+]i oscillations evoked by G protein-coupled receptors require the action of RGS proteins. Inhibition of endogenous RGS protein action disrupted agonist-evoked [Ca2+]i oscillations by a stepwise conversion to a sustained response. Based on these findings and the effect of mutant RGS proteins and anti-RGS protein antibodies on Ca2+ signaling, we propose that RGS proteins within the G protein-coupled receptor complexes provide a biochemical control of [Ca2+]i oscillations.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Substitution / genetics
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Animals
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Calcium / metabolism*
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Calcium Signaling* / drug effects
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Carbachol / pharmacology
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Cells, Cultured
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Cholecystokinin / pharmacology
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Electrophysiology
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Heterotrimeric GTP-Binding Proteins / agonists*
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Heterotrimeric GTP-Binding Proteins / metabolism*
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Inositol 1,4,5-Trisphosphate / metabolism
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Inositol 1,4,5-Trisphosphate / pharmacology
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Macromolecular Substances
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Models, Biological
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Mutation / genetics
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Pancreas / cytology
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Pancreas / drug effects
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Pancreas / metabolism
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RGS Proteins / antagonists & inhibitors
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RGS Proteins / genetics
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RGS Proteins / metabolism*
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Rats
Substances
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Macromolecular Substances
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RGS Proteins
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Inositol 1,4,5-Trisphosphate
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Carbachol
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Cholecystokinin
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Heterotrimeric GTP-Binding Proteins
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Calcium