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A Crucial Role for cAMP and Protein Kinase A in D1 Dopamine Receptor Regulated Intracellular Calcium Transients

Dai R. · Ali M.K. · Lezcano N. · Bergson C.

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Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Ga., USA

Corresponding Author

Clare M. Bergson

Department of Pharmacology and Toxicology, Medical College of Georgia

1459 Laney Walker Blvd

Augusta, GA 30912-2300 (USA)

Tel. +1 706 721 1926, Fax +1 706 721 2347, E-Mail cbergson@mail.mcg.edu

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Neurosignals 2008;16:112–123

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D1-like dopamine receptors stimulate Ca2+ transients in neurons but the effector coupling and signaling mechanisms underlying these responses have not been elucidated. Here we investigated potential mechanisms using both HEK 293 cells that stably express D1 receptors (D1HEK293) and hippocampal neurons in culture. In D1HEK293 cells, the full D1 receptor agonist SKF 81297 evoked a robust dose-dependent increase in Ca2+i following ‘priming’ of endogenous Gq/11-coupled muscarinic or purinergic receptors. The effect of SKF81297 could be mimicked by forskolin or 8-Br-cAMP. Further, cholera toxin and the cAMP-dependent protein kinase (PKA) inhibitors, KT5720 and H89, as well as thapsigargin abrogated the D1 receptor evoked Ca2+ transients. Removal of the priming agonist and treatment with the phospholipase C inhibitor U73122 also blocked the SKF81297-evoked responses. D1R agonist did not stimulate IP3 production, but pretreatment of cells with the D1R agonist potentiated Gq-linked receptor agonist mobilization of intracellular Ca2+ stores. In neurons, SKF81297 and SKF83959, a partial D1 receptor agonist, promoted Ca2+ oscillations in response to Gq/11-coupled metabotropic glutamate receptor (mGluR) stimulation. The effects of both D1R agonists on the mGluR-evoked Ca2+ responses were PKA dependent. Altogether the data suggest that dopamine D1R activation and ensuing cAMP production dynamically regulates the efficiency and timing of IP3-mediated intracellular Ca2+ store mobilization.

© 2008 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: February 05, 2008
Issue release date: February 2008

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 0

ISSN: 1424-862X (Print)
eISSN: 1424-8638 (Online)

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