title: Role of the M2 muscarinic receptor pathway in lidocaine-induced potentiation of the relaxant response to atrial natriuretic peptide in bovine tracheal smooth muscle.
abstract: We earlier reported that lidocaine augments the relaxation and accumulation of guanosine 3',5'-cyclic monophosphate produced by atrial natriuretic peptide (ANP) in bovine tracheal smooth muscle contracted with methacholine. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined the role of muscarinic receptor-mediated signalling in the potentiation of ANP-induced relaxation by lidocaine. Lidocaine (100 micro M) augmented the relaxant responses to ANP in methacholine (0.3 microM)-contracted bovine tracheal smooth muscle but had no effect on the relaxant effects of ANP in preparations contracted with 100 micro M histamine. Treatment of tracheal preparations with methoctramine (0.03 microM), an M2 muscarinic receptor antagonist, enhanced ANP-induced relaxation and this treatment abolished the synergistic action of lidocaine on ANP. In radioligand-binding experiments, lidocaine concentration dependently displaced the specific binding of [3H]- N-methyl scopolamine to cloned human M2 and M3 muscarinic receptors expressed in Chinese hamster ovary cells. These results suggest that lidocaine acts as an M2 muscarinic receptor antagonist, thereby potentiating the relaxant responses to ANP in the bovine tracheal smooth muscle contracted with muscarinic receptor agonists.
authors.affiliation: Department of Molecular PharmacologyKitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, 108-8641, Tokyo, 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: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D009320:Atrial Natriuretic Factor; D008012:Lidocaine