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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1997-10-17
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pubmed:abstractText |
Ethanol inhibits L-type Ca++ channels, but little is known about its effect on other voltage-gated Ca++ channels. To examine non-L-type channels we used nerve growth factor-differentiated PC12 cells treated with the L channel blocker nifedipine. Using selective Ca++ channel antagonists, we found that N-type and P/Q-type channels mediate most of the remaining depolarization-evoked Ca++ rise. Ethanol (10-150 mM) inhibited depolarization-induced rises in intracellular Ca++ with maximal inhibition of 46% achieved using 50 mM ethanol. Inhibition was time dependent, requiring at least 8 min to develop fully. Ethanol did not alter Ca++ mobilization, sequestration, extrusion or capacitative entry. Sp-adenosine cyclic 3',5'-phosphorothioate, a specific activator of protein kinase A (PKA), blocked inhibition by ethanol, whereas the protein kinase C activator phorbol 12-myristate, 13-acetate did not. Okadaic acid, an inhibitor of protein phosphatases type-1 and type-2A, also blocked inhibition by ethanol with an IC50 of 3 nM. This was prevented by inhibiting PKA, indicating that the action of okadaic acid was due to increased PKA-mediated phosphorylation. These results indicate that ethanol can inhibit N-type and P/Q-type channels and this is antagonized by activating PKA. The findings suggest the sensitivity of these channels to ethanol is regulated by a phosphoprotein that is a substrate for PKA and protein phosphatase type-2A.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1487-95
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9316863-Animals,
pubmed-meshheading:9316863-Bradykinin,
pubmed-meshheading:9316863-Calcium,
pubmed-meshheading:9316863-Calcium Channel Blockers,
pubmed-meshheading:9316863-Calcium Channels,
pubmed-meshheading:9316863-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:9316863-Ethanol,
pubmed-meshheading:9316863-PC12 Cells,
pubmed-meshheading:9316863-Potassium,
pubmed-meshheading:9316863-Rats,
pubmed-meshheading:9316863-Sodium
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pubmed:year |
1997
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pubmed:articleTitle |
Protein kinase A regulates regulates inhibition of N- and P/Q-type calcium channels by ethanol in PC12 cells.
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pubmed:affiliation |
Ernest Gallo Clinic & Research Center, University of California, San Francisco, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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