Novel persistent activation of muscarinic M1 receptors by xanomeline.
The muscarinic agonists, xanomeline and carbachol, displayed similar intrinsic activities in stimulating neuronal nitric oxide synthase at muscarinic M1 receptors in Chinese hamster ovary (CHO) cells, with xanomeline being more potent. Pre-incubation (1 h) with 1 microM xanomeline, followed by extensive washing, resulted in a significantly elevated basal response, which was absent on co-incubation with atropine. This phenomenon was not observed with carbachol. This is the first report of a persistent, receptor-activating effect of a muscarinic agonist.
Christopoulos
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Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA. christo@lenti.med.umn.edu
El-Fakahany
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D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology*; D006224:Cricetinae; D004789:Enzyme Activation; D018721:Muscarinic Agonists / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013830:Thiadiazoles / Q000494:pharmacology*; D014162:Transfection
D018721:Muscarinic Agonists; D011725:Pyridines; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D013830:Thiadiazoles; D002217:Carbachol; C075257:xanomeline; D019001:Nitric Oxide Synthase