Effects of lidocaine on cytosolic pH regulation and stimulus-induced effector functions in alveolar macrophages.
Local anesthetics influence a variety of stimulus-induced effector functions in leukocytes. The present study determined the effects of lidocaine on intracellular pH (pHi) regulation, superoxide production, and tumor necrosis factor-alpha (TNF-alpha) release in alveolar macrophages (m phi). Resident m phi were obtained by bronchoalveolar lavage of rabbits. The cells were subjected to an intracellular acid load, and subsequent pHi recovery was followed in the presence or absence of bafilomycin A1, a specific inhibitor of V-type H(+)-translocating ATPase (V-ATPase) or amiloride, an inhibitor of Na+/H+ exchange. Lidocaine slowed pHi recovery in a dose-dependent manner. Pretreatment (1 h) with 2.5 mM lidocaine abolished Na+/H+ exchange and reduced the V-ATPase-mediated component of pHi recovery. Lidocaine also significantly depressed the superoxide production induced by phorbol ester. TNF-alpha release induced by endotoxin was not affected significantly by the local anesthetic. Macrophage viability (trypan blue exclusion) and cellular ATP concentration were unaffected. These results indicate that lidocaine inhibits pHi regulatory mechanisms in alveolar m phi. This disruption of pHi regulation could contribute to inhibitory actions of lidocaine on m phi effector functions.
Bidani
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A
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0876, USA.
Heming
T A
TA
D000136:Acid-Base Equilibrium / Q000187:drug effects* / Q000276:immunology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008012:Lidocaine / Q000494:pharmacology*; D018942:Macrolides; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008297:Male; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000502:physiology; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases
D000779:Anesthetics, Local; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018942:Macrolides; D017923:Sodium-Hydrogen Exchangers; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D000584:Amiloride; C040929:bafilomycin A1; D000255:Adenosine Triphosphate; D008012:Lidocaine; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases