The M3 muscarinic receptor i3 domain confers oxidative stress protection on calcium regulation in transfected COS-7 cells

Aging Cell
J A JosephAleksandra Szprengiel

Abstract

Evidence suggests that muscarinic receptors (MAChRs) are involved in various aspects of neuronal and vascular functioning, and that there is selective oxidative stress sensitivity (OSS) among MAChR subtypes. COS-7 cells transfected with M1, M2 and M4 subtypes show greater OSS than the M1 and M3 subtypes, as seen by the decreased ability of cells to extrude or sequester calcium (Ca(2+)) following exposure to dopamine (DA) or A beta 25-35, and depolarization by oxotremorine. We sought to determine which receptor domain may be responsible for the differential vulnerability to OS between 'OS-sensitive' (M1) and 'non-sensitive' (M3) subtypes. Comparison of the amino acid sequences of each receptor has shown that the third cytoplasmic loop (i3 loop) is the domain with the most variability between the two subtypes. Therefore, mutations were made by either deleting or exchanging the i3 loop of M1 and M3 receptors. Experiments revealed that deletions of the i3 loop increased DA sensitivity (a lower percentage of cells showing recovery of [Ca(2+)](i) following depolarization) in both receptors. Chimerics of M1 in which the i3 loop of the M3 was exchanged with the i3 loop of the M1 (M1M3i3) showed that DA sensitivity was reduced (a greate...Continue Reading

References

Aug 1, 1990·Journal of Neurochemistry·B FornstedtA Carlsson
Jan 1, 1995·Molecular and Chemical Neuropathology·G Ferrari-DiLeoD D Flynn
Dec 1, 1994·Current Opinion in Neurology·D R Lynch, T M Dawson
Sep 1, 1994·Journal of Neurochemistry·Y ChengA Y Sun
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·T G HastingsM J Zigmond
Jul 1, 1996·Neurobiology of Aging·H HartmannW E Müller
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·A I Levey
Apr 29, 1998·The Journal of Biological Chemistry·G WuS M Lanier
Oct 28, 1998·Experimental Gerontology·B Shukitt-HaleJ A Joseph
Apr 29, 1999·Journal of Neuroscience Research·A H StokesK E Vrana
Jul 21, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A ElhusseinyE Hamel
Aug 6, 2000·Cell and Tissue Research·M P MattsonZ F Yu
Aug 26, 2000·European Journal of Epidemiology·D CommengesJ F Dartigues
Feb 13, 2001·Neurobiology of Aging·J JosephM A Smith
Feb 15, 2001·Brain Research. Developmental Brain Research·R C VannucciS J Vannucci
Feb 24, 2001·Journal of Anatomy·E C Toescu, A Verkhratsky
Feb 2, 2002·Free Radical Biology & Medicine·J A JosephJ Strain
Aug 5, 2003·Journal of Alzheimer's Disease : JAD·J A Joseph, D R Fisher

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Citations

Oct 22, 2010·Apoptosis : an International Journal on Programmed Cell Death·Jin-Jun LiuWei-Jin Zang
Jan 24, 2012·Journal of Agricultural and Food Chemistry·Marshall G Miller, Barbara Shukitt-Hale
Aug 2, 2006·Autonomic & Autacoid Pharmacology·J Myslivecek, R Kvetnanský
Sep 28, 2005·Neurochemical Research·J A JosephD Fisher
Feb 25, 2010·Journal of Agricultural and Food Chemistry·James A JosephDerek R Fisher

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