Increase of calmodulin III gene expression by mu-opioid receptor stimulation in PC12 cells

Calmodulin (CaM) is a principal multifunctional mediator of Ca2+ signaling in cells. It is reported that morphine increases CaM contents in mouse brai n. However, the precise mechanism of CaM induction by morphine is unknown. We investigated the changes of CaM by opioid receptor stimulation in mRNA a nd protein levels. Expression of CaM was increased in dose- and time-depend ent manners by morphine with RT-PCR assay in PC12 cells, and naloxone inhib ited the effect of morphine. The expression was also increased with DAMGO ( mu -opioid agonist), but not by DPDPE (delta) and U50488 (kappa). Northern blot analysis revealed that the CaMIII gene was responsive to morphine or D AMGO. CaM protein increased by DAMGO were distributed in both soluble and m embranous fractions in the cells. Taken together, the data suggest that mor phine induces the expression of CaMIII gene through mu -opioid receptor sti mulation.