Differential effects of bupivacaine enantiomers, ropivacaine and lidocaine on up-regulation of cell surface voltage-dependent sodium channels in adrenal chromaffin cells.

摘要: Abstract In cultured bovine adrenal chromaffin cells, (±)-bupivacaine inhibited veratridine-induced 22 Na + influx (IC 50 6.8 μM). The IC of (+)-bupivacaine (2.8 μM) was 6.2-, 7.4-, and 17.1-fold lower than those (−)-bupivacaine (17.3 μM), (−)-ropivacaine (20.6 lidocaine (47.8 Chronic (i.e. 3-h) treatment cells with increased cell surface [ 3 H]saxitoxin ([ H]STX) binding capacity by 48% (EC 233 μM; t 1/2 =7.4 h), without changing the K d value. Treatment for 24 h either (+)- or (−)-bupivacaine, elevated H]STX binding, whereas 24-h had no effect. rise prevented cycloheximide, an inhibitor protein synthesis, brefeldin A, vesicular exit from trans -Golgi network; however, did not increase channel α- β 1 -subunit mRNA levels. subjected to (1 mM h) followed 3-h washout, enhanced, even when measured in presence ouabain, ,K -ATPase. Ptychodiscus brevis toxin-3 potentiated 2.3-fold (±)-bupivacaine-treated as non-treated cells. These results suggest that lipophilic bupivacaine enantiomers acutely inhibit gating, its chronic up-regulates expression channels via translational externalization events.