Valium Research Today is a free monthly online journal that collates and summarizes the latest research about Valium, including details on diazepam, depression, side-effects, withdrawal. | ||||||||
|
Activation of protein kinase C reduces benzodiazepine potency at GABAA receptors in NT2-N neurons.Gao L, Greenfield LJ Cellular and Molecular Neurobiology Program and Department of Neurology, Medical College of Ohio, 3120 Glendale Avenue, Toledo, OH 43614, USA. Phosphorylation of GABA(A) receptors (GABARs) by protein kinase C (PKC) modulates GABAR function and allosteric enhancement by benzodiazepines and barbiturates. However, the effects of phosphorylation have been inconsistent, possibly due to variability in neuron or GABAR populations. We used NT2-N neurons to address this issue in a more homogeneous cell population. Whole-cell and gramicidin "perforated-patch" recordings were used to analyze changes in GABAR currents induced by preincubation with 4beta-phorbol-12,13-dibutyrate (PDBu), the inactive 4alpha-phorbol-didecanoate (4alpha-PDD) or bisindolylmaleimide (BIM, a PKC inhibitor). PDBu, but not 4alpha-PDD, caused a rightward shift of the concentration-response curve (C/R) for diazepam enhancement, without affecting maximal enhancement. BIM blocked the rightward shift of the diazepam C/R induced by PDBu. PDBu did not alter the GABA C/R or the current reversal potential. The PKC effect was specific to the benzodiazepine site, as PDBu did not alter potentiation of GABAR currents by pentobarbital. Exposure to diazepam (10 microM) for 7 days reduced maximal diazepam enhancement without affecting the EC(50); PDBu also caused a small rightward shift of the diazepam EC(50) in these cells. PKC activation reduced the apparent affinity of diazepam at NT2-N GABARs without altering maximal enhancement, suggesting decreased allosteric coupling of the benzodiazepine and GABA sites. Published 21 February 2005 in Neuropharmacology, 48(3): 333-42.
© 2004-2008 Valium Research Today. All Rights Reserved. |
| ||||||
