Tyrosine kinase phosphorylation of GABA(A) receptor alpha1, beta2 and gamma2 subunits following chronic intermittent ethanol (CIE) exposure of cultured cortical neurons of mice.
There is evidence that many of the GABA(A) receptor subunits contain consensus sequence for tyrosine kinase, and phosphorylation may play a key role in ethanol's regulation of GABA(A) receptors. Recently, we investigated the effect of chronic exposure of ethanol (CE) on tyrosine kinase phosphorylation and reported that there was an up-regulation in tyrosine kinase phosphorylation of the beta(2)- and gamma(2)- subunits and no effect on alpha(1)-subunit of the GABA(A) receptor in the cultured cortical neurons of mice. In the present study, we have further investigated the effect of chronic intermittent administration of ethanol (CIE) on tyrosine kinase phosphorylation of the GABA(A) receptor subunits (alpha(1), beta(2), and gamma(2)) in the mouse cultured cortical neurons by immunoprecipitation and Western blot techniques. We observed that there was an up-regulation in the tyrosine kinase phosphorylation of the GABA(A )receptor beta(2)- and gamma(2)-subunits following CIE exposure, and no effect on alpha(1)-subunit in the cultured cortical neurons of mice. These CIE changes, unlike CE, were not reverted back to the control level following ethanol withdrawal even after 7 days. Acute exposure of ethanol did not cause any change in the tyrosine kinase regulation of the GABA(A) receptor subunits. In conclusion, the CIE exposure, unlike chronic/acute ethanol exposure, regulates the tyrosine kinase phosphorylation of the selective population of GABA(A )receptors in a long lasting manner.
Ravindran
C R Marutha
CR
Department of Pharmacology, The University of Texas Health Science Center, 7703 Floyd Curl MC 7764 Dr., San Antonio, TX 78229-3900, USA. ticku@uthscsa.edu
Ticku
Maharaj K
MK
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D021122:Protein Subunits / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018079:Receptors, GABA; D011963:Receptors, GABA-A / Q000378:metabolism*
C546241:Gabra1 protein, mouse; C470436:Gabrb2 protein, mouse; C546280:Gabrg2 protein, mouse; D021122:Protein Subunits; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D000431:Ethanol; D011505:Protein-Tyrosine Kinases