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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Martinez, L. D. Wick, M. J. Mascia, M. P. Harris, R. A. |
| Description | Author Affiliation: Mascia MP ( Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.) |
| Abstract | 1. The effects of several kinase inhibitors (staurosporine, GF 109203X, H89, KN62, genistein) and of the phosphatase inhibitor calyculin A were studied on the ethanol potentiation and on the function of homomeric alpha1 glycine receptor expressed in Xenopus oocytes using a two electrode voltage clamp recording technique. 2. The function of the homomeric alpha1 glycine receptor was not modified in Xenopus oocytes pretreated with kinase inhibitors or with the phosphatase inhibitor calyculin A. 3. The potentiation of the glycine receptor function induced by ethanol (10-200 mM) was significantly reduced in Xenopus oocytes pretreated with the PKC inhibitors staurosporine or GF 109203X. 4. No differences in propofol (2.5 microM) or halothane (250 microM) actions were found after exposure of Xenopus oocytes to staurosporine. 5. No differences in ethanol sensitivity were found after exposure of Xenopus oocytes expressing glycine alpha1 receptors to H89, KN62, genistein or to the phosphatase inhibitor calyculin A. 6. The mutant alpha1 (S391A), in which the PKC phosphorylation site at serine 391 was mutated to alanine, was less sensitive to the effects of ethanol than was the alpha1 wild type receptor. Moreover, the ethanol potentiation of the glycine receptor function was not affected by treatment with staurosporine in oocytes expressing alpha1 (S391A). 7. The splice variant of the alpha1 glycine receptor subunit, alpha1ins, containing eight additional amino acids and a potential phosphorylation site for PKA, did not differ from wild type for sensitivity to ethanol. 8. These results indicate that phosphorylation by PKC of the homomeric alpha1 glycine receptor subunit modulates ethanol potentiation, but not the function of the glycine receptor. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 125 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1998-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Ethanol Pharmacology Protein Kinase C Antagonists & Inhibitors Receptors, Glycine Drug Effects Animals Cloning, Molecular Dose-Response Relationship, Drug Enzyme Inhibitors Glycine Glycine Agents Halothane Indoles Maleimides Oocytes Oxazoles Phosphoprotein Phosphatases Phosphorylation Propofol Metabolism Genetics Staurosporine Strychnine Xenopus Laevis Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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