Lidocaine attenuates muscarinic receptor-mediated inhibition of adenylyl cyclase in airway smooth muscle.
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.
Yunoki
Motonari
M
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Nakahara
Tsutomu
T
Mitani
Akiko
A
Maruko
Takeshi
T
Kubota
Yuko
Y
Sakamoto
Kenji
K
Ishii
Kunio
K
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
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D011976:Receptors, Muscarinic; D008012:Lidocaine; D000262:Adenylyl Cyclases