We have investigated the mechanisms regulating the expression of the μ-opioid receptor, using P19 mouse embryonal carcinoma cells, which normally lack this receptor, but which can be induced to express it in aggregated cells by retinoic acid treatment. The expression level of μ-opioid receptor mRNA was found to be closely correlated with aggregation status, and more specifically by cell to cell interaction requiring neural cell adhesion molecules (NCAM). We showed that NCAM activates the μ-opioid receptor gene through a pathway involving phospholipase C-arachidonic acid-calcium channel-calcium/calmodulin kinase II. A similar pathway was previously shown to promote neurite outgrowth, however, with distinct specificity, including the role of calcium channels. Activation of L-type calcium channels elevated μ-opioid receptor expression, while N-type-channel activity had the opposite effect. The effect of anti-NCAM-antibody treatment was not due to retardation of general neural development and was specific to the μ-opioid receptor gene. Our results indicate that the P19 system is an useful model to study the expression of the μ-opioid receptor gene.
Bibliographical noteFunding Information:
This research was supported by National Institutes of Health research Grants DA00564, DA01583, DA11806 and DA70554, and the F. and A. Stark Fund of the Minnesota Medical Foundation.
- Gene expression
- Neural cell adhesion molecule
- Neurite outgrowth
- Opioid receptor