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Mutation of Putative Phosphorylation Sites in the 5-Hydroxytryptarnine3 Receptor Does Not Eliminate Its Modulation by Ethanol.
- Source :
- Alcoholism: Clinical & Experimental Research; 1999, Vol. 23 Issue 1, p12-17, 6p
- Publication Year :
- 1999
-
Abstract
- The function of the 5-hydroxytryptamine<subscript>3</subscript> (5-HT<subscript>3</subscript>) receptor is enhanced by ethanol, but the amino acid residue(s) that confers sensitivity to ethanol remains to be identified. Phosphorylation of the related GABA<subscript>A</subscript> receptor has been implicated in conferring its sensitivity to ethanol. In common with the GABA<subscript>A</subscript> receptor, the 5-HT<subscript>3</subscript> receptor contains multiple consensus sites for protein kinases. To evaluate the possibility that phosphotylation of the 5-HT<subscript>3</subscript> receptor underlies its ethanol sensitivity, we examined the ability of ethanol to enhance 5-HT-mediated currents in a mutant 5-HT<subscript>3</subscript> receptor containing no intracellular serines, threonines, or tyrosines. Mutation of these 13 residues in the intracellular loops produced a modest leftward shift in the 5-HT concentration response curve, with the EC<subscript>50</subscript>'s for 5-HT decreasing from 0.839 ± 0.03 μM in the wild-type receptor to 0.713 ± 0.03 μM in the mutant receptor. Cooperativity of the 5-HT binding sites was enhanced by the mutations, with Hill coefficients of 2.92 for the wild-type receptor and 3.74 for the mutant receptor, respectively. In oocytes expressing mutant receptors, ethanol (50 to 200 mM) enhanced the currents produced by low concentrations of 5-HT by ∼5 to 45%, which was not statistically different from the potentiation produced by ethanol in wild-type receptors. These results suggest that ethanol enhancement of the 5-HT<subscript>3</subscript> receptor function does not require receptor phosphorylation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- Volume :
- 23
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Alcoholism: Clinical & Experimental Research
- Publication Type :
- Academic Journal
- Accession number :
- 91183369
- Full Text :
- https://doi.org/10.1111/j.1530-0277.1999.tb04018.x