title: Lidocaine attenuates muscarinic receptor-mediated inhibition of adenylyl cyclase in airway smooth muscle.
abstract: We examined how lidocaine affects muscarinic receptor-mediated inhibition of adenylyl cyclase in bovine tracheal smooth muscles. Lidocaine (100 microM) augmented the relaxant responses to forskolin in the bovine tracheal smooth muscle contracted with methacholine (0.3 microM). On the other hand, lidocaine failed to affect the relaxant effects of forskolin on the histamine (100 microM)- and KCl (40 mM)-contracted preparations. Lidocaine (100 microM) enhanced both basal and forskolin-stimulated cAMP accumulation in the presence of methacholine (0.3 microM). However, in the absence of methacholine, neither basal nor forskolin-stimulated cAMP accumulation was affected by lidocaine. Similar phenomenon was observed when the bovine tracheal smooth muscles were treated with methoctramine (0.03 microM). In radioligand binding experiments, lidocaine inhibited [3H]N-methyl scopolamine binding to cloned human muscarinic receptors (M(1)-M(5)) expressed in Chinese hamster ovary cells. These results suggest that lidocaine prevents muscarinic receptor-mediated signaling pathway and thereby reverses inhibition of adenylyl cyclase by methacholine in bovine tracheal smooth muscle.
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Motonari
authors.initials: M
authors.lastname: Yunoki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakahara
authors.forename: Akiko
authors.initials: A
authors.lastname: Mitani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Maruko
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D011976:Receptors, Muscarinic; D008012:Lidocaine; D000262:Adenylyl Cyclases