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Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward.
Neuron
September 2015
Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address:
The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown.
View Article and Find Full Text PDFActivation and modulation of concatemeric GABA-A receptors expressed in human embryonic kidney cells.
Mol Pharmacol
June 2009
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
We have employed whole-cell and single-channel electrophysiology to examine the kinetic and pharmacological properties of GABA-A receptors consisting of gamma2L-beta2-alpha1 and beta2-alpha1 subunit concatemeric constructs expressed in human embryonic kidney cells. Concatemeric receptors activated by GABA exhibited the same single-channel conductance, channel opening rate constant, and basic open- and closed-time properties as receptors containing free subunits. However, the whole-cell GABA dose-response and the single-channel effective opening rate curves were shifted to higher GABA concentrations, suggesting that the concatemeric receptors have a lower affinity to GABA.
View Article and Find Full Text PDFGalantamine activates muscle-type nicotinic acetylcholine receptors without binding to the acetylcholine-binding site.
J Neurosci
February 2005
Department of Anesthesiology, Washington University, St. Louis, Missouri 63110, USA.
Galantamine (Reminyl; Janssen Pharmaceutica, Titusville, NJ) belongs to a class of acetylcholinesterase inhibitors approved for symptomatic treatment of Alzheimer's disease. The drug presumably acts by raising and prolonging the profile of acetylcholine (ACh) via an inhibitory effect on the esterase. However, there is also evidence demonstrating that galantamine can activate the nicotinic ACh receptor or modulate its activation by ACh.
View Article and Find Full Text PDFActivation of GABA(A) receptors containing the alpha4 subunit by GABA and pentobarbital.
J Physiol
April 2004
Department of Anaesthesiology, Washington University in St Louis, Campus Box 8054, 660 S. Euclid Ave, St Louis, MO 63110, USA.
The activation properties of GABA(A) receptors containing alpha4beta2gamma2 and alpha4beta2delta subunits were examined in the presence of GABA or pentobarbital. The receptors were expressed transiently in HEK 293 cells, and the electrophysiological experiments were carried out using cell-attached single-channel patch clamp or whole-cell macroscopic recordings. The data show that GABA is a stronger activator of alpha4beta2gamma2 receptors than alpha4beta2delta receptors.
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