Lidocaine potentiates the relaxant effects of cAMP-elevating agents in bovine tracheal smooth muscle.
The effect of lidocaine on the relaxation and accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) induced by salbutamol, forskolin and 3-isobutyl-1-methylxanthine (IBMX) was examined in bovine tracheal smooth muscle preparations precontracted with methacholine (0.3 microM). Lidocaine attenuated the methacholine-induced contraction in a concentration-dependent manner. Pretreatment of the preparations with lidocaine (100 microM) caused significant leftwards shifts of concentration/response curves for the relaxant responses to salbutamol, forskolin, and IBMX, whereas it did not change the responses to diltiazem. Similar leftwards shifts were observed when the preparations were treated with procaine (6 microM) or bupivacaine (40 microM). Lidocaine (100 microM) augmented cAMP accumulation induced by salbutamol (10 nM) and forskolin (1 microM). These results suggest that lidocaine augments the relaxant responses to cAMP-elevating agents through enhancement of cAMP accumulation.
Nakahara
T
T
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan. nakaharat@pharm.kitasato-u.ac.jp
Yunoki
M
M
Moriuchi
H
H
Sakamato
K
K
Ishii
K
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D014132:Trachea / Q000033:anatomy & histology / Q000187:drug effects*
D000779:Anesthetics, Local; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D011343:Procaine; D008012:Lidocaine; D000242:Cyclic AMP; D000420:Albuterol; D015056:1-Methyl-3-isobutylxanthine; D002045:Bupivacaine