title: Effects of lidocaine on sarcolemmal fluidity and cellular cAMP in rat cardiomyocytes.
abstract: Antiarrhythmic drugs with local anesthetic properties modify the physical state of membrane phospholipids and could change adenylate cyclase activity and, thus, influence cardiac ischemic arrhythmias. Adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cardiomyocytes cultured from newborn rat and fluorescence anisotropy of sarcolemma-enriched membranes were investigated in the presence of a neutral anesthetic drug benzyl alcohol and of a cationic anesthetic drug lidocaine. Benzyl alcohol increased in a dose-dependent manner both sarcolemma fluidity and isoproterenol- or cholera toxin-stimulated cAMP accumulation. In contrast, benzyl alcohol inhibited cAMP accumulation in forskolin-stimulated cells. Lidocaine induced a dose-related inhibition of isoproterenol-, forskolin-, and cholera toxin-stimulated cAMP accumulation without eliciting any change in sarcolemma fluidity. The inhibitory effect of lidocaine on isoproterenol-stimulated cAMP accumulation was reversed when cells were pretreated with pertussis toxin. These data suggest that the inhibitory effect of lidocaine on cAMP synthesis might involve a polar interaction with the Gi regulatory subunit of adenylate cyclase. Such an effect could contribute, in vivo, to both the antiarrhythmic and the negative inotropic effect of lidocaine.
authors.affiliation: U. 251, Département de Physiologie, Faculté de Médecine X. Bichat, Université Paris VII, France.
authors.forename: S
authors.initials: S
authors.lastname: Roux
authors.forename: B
authors.initials: B
authors.lastname: Escoubet
authors.forename: G
authors.initials: G
authors.lastname: Friedlander
authors.forename: C
authors.initials: C
authors.lastname: Le Grimellec
authors.forename: I
authors.initials: I
authors.lastname: Bertrand
authors.forename: C
authors.initials: C
authors.lastname: Amiel
mesh_terms: D037361:Adenylate Cyclase Toxin; D000818:Animals; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000494:pharmacology; D002413:Cations, Divalent; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005454:Fluorescence Polarization; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D001592:Benzyl Alcohols; D002413:Cations, Divalent; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D008012:Lidocaine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007545:Isoproterenol; D019905:Benzyl Alcohol