Up-regulated L-type high voltage-gated calcium channels cause increase in diazepam binding inhibitor induced by sustained morphine exposure in mouse cerebrocortical neurons

Abstract

Mechanisms of increase in diazepam binding inhibitor (DBI) mRNA expression in mouse cerebrocortical neurons after sustained morphine exposure were investigated. Increases in DBI and its mRNA expressions induced by sustained morphine (0.3 microM) exposure for 3 days were completely abolished by naloxone and nifedipine, but not by omega-agatoxin VIA and omega-conotoxin GIVA. Increase in [(3)H]diltiazem binding to the particulate fractions from the morphine-treated neurons was due to increased B(max) value with no changes in K(d) value. Western blot analysis on L-type high voltage-gated calcium channel (HVCC) subunits revealed the increased expressions of alpha1C, alpha1D, and alpha2/delta1 subunits and decreased of beta4 subunit expression, whereas expression of N- and P/Q-type HVCC subunits was not changed. These results indicate that morphine-induced increase in DBI mRNA expression is mediated via increased Ca(2+) entry through up-regulated L-type HVCCs.