Nicotine-induced up-regulation and desensitization of alpha4beta2 neuronal nicotinic receptors depend on subunit ratio

The Journal of Biological Chemistry
Gretchen Y López-HernándezJosé A Lasalde-Dominicci

Abstract

Desensitization induced by chronic nicotine exposure has been hypothesized to trigger the up-regulation of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) in the central nervous system. We studied the effect of acute and chronic nicotine exposure on the desensitization and up-regulation of different alpha4beta2 subunit ratios (1alpha:4beta, 2alpha:3beta, and 4alpha:1beta) expressed in Xenopus oocytes. The presence of alpha4 subunit in the oocyte plasmatic membrane increased linearly with the amount of alpha4 mRNA injected. nAChR function and expression were assessed during acute and after chronic nicotine exposure using a two-electrode voltage clamp and whole-mount immunofluorescence assay along with confocal imaging for the detection of the alpha4 subunit. The 2alpha4:3beta2 subunit ratio displayed the highest ACh sensitivity. Nicotine dose-response curves for the 1alpha4:4beta2 and 2alpha4:3beta2 subunit ratios displayed a biphasic behavior at concentrations ranging from 0.1 to 300 microm. A biphasic curve for 4alpha4:1beta2 was obtained at nicotine concentrations higher than 300 microm. The 1alpha4:4beta2 subunit ratio exhibited the lowest ACh- and nicotine-induced macroscopic current, whereas 4alpha4:1beta...Continue Reading

References

Jun 1, 1990·Trends in Pharmacological Sciences·S Wonnacott
Jan 1, 1993·Annual Review of Neuroscience·P B Sargent
Nov 1, 1994·Addiction·D J Balfour
May 1, 1996·Neuron·J A Dani, S Heinemann
Dec 13, 1997·Molecular Neurobiology·J Lindstrom
Dec 18, 1998·Neuron·J P Changeux, S J Edelstein
Nov 19, 2002·Journal of Neurobiology·Michael W Quick, Robin A J Lester
Jan 16, 2003·Molecular Pharmacology·Mark E NelsonJon Lindstrom

❮ Previous
Next ❯

Citations

Jun 8, 2007·Cellular and Molecular Neurobiology·Enrique L M Ochoa, Jose Lasalde-Dominicci
Sep 27, 2008·Cellular and Molecular Neurobiology·Gretchen Y López-HernándezJosé A Lasalde-Dominicci
Jul 9, 2013·Biochemical Pharmacology·Sara Francesca ColomboCecilia Gotti
Jun 28, 2005·Trends in Neurosciences·Rashid GiniatullinJerrel L Yakel
Apr 16, 2010·The Journal of Biological Chemistry·Lorise C GahringScott W Rogers
Dec 23, 2008·American Journal of Respiratory Cell and Molecular Biology·Xiao Wen FuEliot R Spindel
Oct 9, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cheng XiaoHenry A Lester
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Gregg B Wells
Apr 8, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Miriam Melis, Marco Pistis
May 6, 2006·European Journal of Pharmacology·Ruud ZwartEmanuele Sher
Aug 1, 2006·Trends in Pharmacological Sciences·Cecilia GottiFrancesco Clementi
Oct 18, 2006·Journal of Neuroscience Research·Madeline Nieves-CintrónJosé A Lasalde-Dominicci
Sep 22, 2005·The Journal of Biological Chemistry·Alexandra M PersonGregg B Wells
Oct 15, 2005·The Journal of Pharmacology and Experimental Therapeutics·Jun HuJie Wu
Jan 15, 2011·British Journal of Pharmacology·Thomas E WootersLinda P Dwoskin
Sep 6, 2020·Reviews in the Neurosciences·Zeyi HuangSijie Tan

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.