title: Effect of carticaine on the sarcoplasmic reticulum Ca2+-dependent adenosine triphosphatase.
abstract: The sarcoplasmic reticulum Ca2+-ATPase (calcium-dependent adenosine triphosphatase) transports Ca2+ from the myoplasm to the reticulum lumen at the expense of free energy from ATP hydrolysis. Carticaine is a local anesthetic of frequent use in dentistry which is now entering other clinical fields. We studied the action of carticaine on the sarcoplasmic reticulum (SR) skeletal muscle Ca2+-ATPase. SR vesicles from rabbit fast skeletal muscle were used. Carticaine inhibits the enzymatic activity. The inhibition of the enzymatic activity depends on pH, [Ca2+] and the presence of calcimycin. Half-maximal carticaine concentration that inhibits the ATPase activity tends to a maximal value upon increasing [Ca2+]. Carticaine concentrations required to inhibit the enzymatic activity at myoplasmic calcium concentration are lower than usual clinical doses: Ki=6.0+/-1.4 mM carticaine (n=5) for 0.1 microM [Ca2+]. ATP-dependent calcium uptake is also inhibited by the local anesthetic: Ki=30.5+/-3.4 mM (n=4). Besides, carticaine inhibits the phosphorylation of the enzyme by inorganic phosphate (Pi): Ki=20.0+/-3.4 (n=5) - 33.2+/-4.6 (n=4) mM, for [Pi] 1-4 mM. Carticaine increases the membrane permeability to Ca2+. Ca2+ efflux from preloaded vesicles is prevented by Ca2+ and Mg2+. Our results suggest that the diffusion of the local anesthetic into muscle fibers might trigger undesired effects such as sustained contraction of the masticatory muscles.
authors.affiliation: Cátedra de Biofísica, Facultad de Odontología, Universidad de Buenos Aires, Argentina. delia@biofis.odon.uba.ar
authors.forename: D
authors.initials: D
authors.lastname: Takara
authors.forename: G A
authors.initials: GA
authors.lastname: Sánchez
authors.forename: G L
authors.initials: GL
authors.lastname: Alonso
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002355:Carticaine / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011817:Rabbits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: D000779:Anesthetics, Local; D007476:Ionophores; D010710:Phosphates; D000001:Calcimycin; D002355:Carticaine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium