title: Enhancement of maximal activation of neuronal nitric oxide synthase at muscarinic M1 receptors following prolonged agonist treatment.
abstract: It was previously believed that the neuronal type of nitric oxide (NO) synthase was constitutive in nature, and that changes in the concentration of intracellular Ca2+ represent the sole input that regulates its activity. Recent reports, however, suggested that this enzyme could also be induced under certain conditions. We report here that prolonged stimulation of M1 muscarinic acetylcholine receptors results in potentiation of maximal receptor-mediated activation of neuronal NO synthase in Chinese hamster ovary cells. This effect was dependent on the concentration of agonist during the treatment and was abolished by a muscarinic receptor antagonist. These findings are important for understanding the sequelae of prolonged administration of muscarinic agonists in vivo.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Cuadra
authors.forename: E E
authors.initials: EE
authors.lastname: El-Fakahany
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D018721:Muscarinic Agonists / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010890:Pirenzepine / Q000494:pharmacology; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D002217:Carbachol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I