Novel regulation of p38gamma by dopamine D2 receptors during hypoxia.
The p38 signalling pathway is part of the MAPK superfamily and is activated by various stressors. Our previous results have shown that two p38 isoforms, p38alpha and p38gamma, are activated by hypoxia in the neural-like PC12 cell line. PC12 cells also synthesize and secrete catecholamines, including dopamine, in response to hypoxia. We have now used this system to study the interaction between D2-dopamine receptor signalling and the p38 stress-activated protein kinases. Our results show that two D2 receptor antagonists, butaclamol and sulpiride, enhance hypoxia-induced phosphorylation of p38gamma, but not p38. This effect persists in protein kinase A (PKA)-deficient PC12 cells, demonstrating that p38gamma modulation by the D2 receptor is independent of the cAMP/PKA signalling system. We further show that removal of extracellular calcium blocks the hypoxia-induced increase in p38gamma activity. These results are the first to demonstrate that p38gamma can be regulated by the D2 receptor and calcium following hypoxic exposure.
Conrad
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College of Medicine, Department of Molecular and Cellular Physiology, University of Cincinnati, P.O. Box 67-0576, Cincinnati, OH 45267-0576, USA.
Millhorn
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Beitner-Johnson
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D000818:Animals; D015153:Blotting, Western; D002069:Butaclamol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D000860:Hypoxia; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D016716:PC12 Cells; D010766:Phosphorylation; D020033:Protein Isoforms; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015398:Signal Transduction; D013469:Sulpiride / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D018492:Dopamine Antagonists; D020033:Protein Isoforms; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D002069:Butaclamol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium; D004298:Dopamine