Journal article

Regulation of M-2 muscarinic acetylcholine receptor expression and signaling by prolonged exposure to allosteric modulators

LT May, Y Lin, PM Sexton, A Christopoulos

Journal of Pharmacology and Experimental Therapeutics | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | Published : 2005

Abstract

The effects of prolonged exposure of M(2) muscarinic acetylcholine receptors (mAChRs), stably expressed in Chinese hamster ovary cells, to the allosteric modulators gallamine, alcuronium, and heptane-1,7-bis (dimethyl-3'-phthalimidopropyl)-ammonium bromide (C(7)/3'-phth) were compared with the effects of the agonist carbachol (CCh) and antagonists atropine and N-methylscopolamine (NMS). Intact cell saturation binding assays using [(3)H]NMS found that pretreatment of the cells for 24 h with CCh caused a significant down-regulation of receptor number, whereas atropine, NMS, and all three allosteric modulators caused receptor up-regulation. Functional assays using a cytosensor microphysiometer ..

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