Reversible inhibition of Ca2+- or Mg2+-dependent ATPase activity in the rat brain by local anesthetics

Background: Local anesthetics can easily pass through the blood-brain barrier and may cause adverse effects in the brain; however, the direct influence of these effects on the central nervous system remains to be clarified. ATPases activated by Ca2+ (Ca-ATPase) or Mg 2+ (Mg-ATPase), which are different from the plasma membrane (PMCA) or the sarco-endoplasmic reticulum (SERCA) Ca, Mg-ATPases, exist in the brain. There are some reports on the effect of local anesthetics on PMCA and SERCA, but few have described the effects on Ca- or Mg-ATPase. The aim of our study was to describe the effect of local anesthetics on these ATPases. Methods: We isolated plasma membrane (PII) and microsomal (PIII) fractions from rat brain homogenates and examined the effects of local anesthetics, procaine, tetracaine, lidocaine, prilocaine, bupivacaine, and dibucaine on Ca- or Mg-ATPase activities at pH 7.4 or 9.5. Results: The Ca- and Mg-ATPase activities of the PII fraction were inhibited in a dose-dependent manner by all local anesthetics at pH 9.5, which is the range of clinical use. Tetracaine and dibucaine, which are clinically strong anesthetics, showed strong inhibitory effects on ATPase activity. The inhibition of activity by lidocaine, tetracaine, and dibucaine was recovered after their concentrations were diluted, suggesting that their inhibitory actions were reversible. Conclusion: These results suggest that local anesthetics at concentrations available for dental use, reversibly inhibit PII Ca- or Mg-ATPase activities in the rat brain