Lidocaine inhibits stimulation-coupled responses of neutrophils and protein kinase C activity.
The effects of lidocaine, a local anesthetic, on various stimulation-coupled responses of neutrophils were studied. Superoxide generation, generation of chemiluminescence, depolarization of membrane potential and transitional increase in intracellular Ca2+ were inhibited by lidocaine in a concentration dependent manner. Lidocaine also inhibited Ca(2+)-activated phospholipid-dependent protein kinase (PKC) in the presence of various concentrations of Ca2+, phosphatidylserine and dioleoylglycerol. For the inhibition of all these stimulation-coupled responses, a similar order of the lidocaine concentration was needed. As in the case of dibucaine (Mori, T., Takai, Y., Minakuchi, R., Yu, B. and Nishizuka, Y., J. Biol. Chem. 255:8378-8380, 1980), lidocaine inhibited PKC activity in a manner competitive with phosphatidylserine. Lidocaine also inhibited the phosphorylation of 47 kDa neutrophil cytosplasmic protein, a phosphorylated protein required for NADPH oxidase activation. Thus, the cellular membrane phospholipid may be one of the target sites of lidocaine for the inhibitory action on the various stimulation-coupled responses of neutrophils, and these effects of lidocaine may correlate with its inhibitory action on PKC activity.
Tomoda
M K
MK
Department of Anesthesiology, Kochi Medical School, Japan.
Tsuchiya
M
M
Ueda
W
W
Hirakawa
M
M
Utsumi
K
K
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008081:Liposomes / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism
D008081:Liposomes; D011506:Proteins; D013481:Superoxides; D008012:Lidocaine; D011493:Protein Kinase C; D002118:Calcium