NDLI: Pharmacological assessment of m1 muscarinic acetylcholine receptor-gq/11 protein coupling in membranes prepared from postmortem human brain tissue.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Salah-Uddin, Hasib Thomas, David R. Davies, Ceri H. Hagan, Jim J. Wood, Martyn D. Watson, Jeannette M. Challiss, R. A. John
Description	Country affiliation: United kingdom Author Affiliation: Salah-Uddin H ( Department of Cell Physiology and Pharmacology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, United Kingdom.)
Abstract	Using a selective Galpha(q/11) protein antibody capture guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding approach, it has been possible to perform a quantitative pharmacological examination of the functional activity of the M(1) muscarinic acetylcholine receptor (mAChR) in membranes prepared from human postmortem cerebral cortex. Oxotremorine-M caused a > or = 2-fold increase in [35S]GTPgammaS-Galpha(q/11) binding with a pEC(50) of 6.06 +/- 0.16 in Brodmann's areas 23 and 25 that was almost completely inhibited by preincubation of membranes with the M(1) mAChR subtype-selective antagonist muscarinic toxin-7. In addition, the orthosteric and allosteric agonists, xanomeline [3(3-hexyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine] and AC-42 (4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine hydrogen chloride), increased [35S]-GTPgammaS-Galpha(q/11) binding, but with reduced intrinsic activities, inducing maximal responses that were 42 +/- 1 and 44 +/- 2% of the oxotremorine-M-induced response, respectively. These data indicate that the M(1) receptor is the predominant mAChR subtype coupling to the Galpha(q/11) G protein in these brain regions and that it is possible to quantify the potency and intrinsic activity of full and partial M(1) mAChR receptor agonists in postmortem human brain using a selective Galpha(q/11) protein antibody capture [35S]GTPgammaS binding assay.
File Format	HTM / HTML
ISSN	00223565
Issue Number	3
Volume Number	325
e-ISSN	15210103
Journal	Journal of Pharmacology and Experimental Therapeutics
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2008-06-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Membranes Humans Antibodies Rats Rats, Sprague-dawley Cerebral Cortex Sulfur Radioisotopes Muscarinic Antagonists Metabolism Receptor, Muscarinic M1 Discipline Pharmacology Guanosine 5'-o-(3-thiotriphosphate) Antagonists & Inhibitors Journal Article Muscarinic Agonists Animals Discipline Therapeutics Gtp-binding Protein Alpha Subunits, Gq-g11 Atropine Elapid Venoms Female Agonists Aged
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

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