title: Inhibition of cyclic AMP formation in N1E-115 neuroblastoma cells is mediated by a non-cardiac M2 muscarinic receptor subtype.
abstract: The cardioselective muscarinic antagonist, AF-DX 116 [11[2-[(diethyl-amino)-methyl]-O-1-piperidinyl]-5,11-dihydro-6H-pyrido- [2,3-b][1,4]-benzodiazepine-6-one), was weak at blocking the M2 muscarinic receptor-mediated inhibition of cyclic adenosine monophosphate (cAMP) formation in mouse neuroblastoma cells (clone N1E-115). In contrast, the glandular-selective antagonists, hexahydro-sila-difenidol (HHSiD) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), were quite potent at inhibiting this response, being 14- and 318-fold more potent than AF-DX 116 in this regard, respectively. According to the rank order of potency of these two classes of antagonists, these data provide the first pharmacological evidence that inhibition of cAMP formation in a neuronal tissue is mediated by a non-cardiac M2 muscarinic receptor subtype.
authors.affiliation: Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore 21201.
authors.forename: W
authors.initials: W
authors.lastname: Surichamorn
authors.forename: C L
authors.initials: CL
authors.lastname: Amrhein
authors.forename: C
authors.initials: C
authors.lastname: Forray
authors.forename: E E
authors.initials: EE
authors.lastname: el-Fakahany
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000378:metabolism*; D051379:Mice; D018727:Muscarinic Antagonists; D019832:N-Methylscopolamine; D009447:Neuroblastoma; D010880:Piperidines / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000145:classification / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018727:Muscarinic Antagonists; D010880:Piperidines; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D000242:Cyclic AMP; C046773:hexahydrosiladifenidol; D019832:N-Methylscopolamine