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mu-Opioid receptor gene expression: the role of NCAM
1Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455-0217, USA.
Abstract:
We have investigated the mechanisms regulating the expression of the mu-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 mu-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 mu-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 mu-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 mu-opioid receptor gene. Our results indicate that the P19 system is an useful model to study the expression of the mu-opioid receptor gene.
Insights
Neural cell adhesion molecules (NCAM) regulate mu-opioid receptor expression in P19 cells via a specific signaling pathway. This pathway involves phospholipase C, arachidonic acid, and calcium channels, highlighting a novel mechanism for receptor gene regulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Mu-opioid receptors are crucial in pain modulation and addiction.
- Understanding their gene expression regulation is vital for therapeutic development.
- P19 mouse embryonal carcinoma cells offer a model to study induced receptor expression.
Purpose of the Study:
- To elucidate the molecular mechanisms controlling mu-opioid receptor gene expression.
- To identify key signaling molecules and cellular interactions involved in receptor upregulation.
- To validate the P19 cell system as a model for studying mu-opioid receptor regulation.
Main Methods:
- Utilized P19 mouse embryonal carcinoma cells induced with retinoic acid.
- Assessed mu-opioid receptor mRNA levels correlating with cell aggregation.
- Investigated the role of neural cell adhesion molecules (NCAM) and downstream signaling pathways.
- Examined the specific effects of L-type and N-type calcium channel activity.
Main Results:
- Mu-opioid receptor mRNA expression strongly correlated with cell aggregation and NCAM-mediated cell-cell interactions.
- NCAM activates the mu-opioid receptor gene via a phospholipase C-arachidonic acid-calcium channel-calcium/calmodulin kinase II pathway.
- L-type calcium channel activation increased receptor expression, whereas N-type channel activity decreased it.
- Anti-NCAM antibody treatment specifically affected mu-opioid receptor gene expression without impacting general neural development.
Conclusions:
- NCAM signaling is a key regulator of mu-opioid receptor gene expression in developing neural cells.
- The P19 cell system provides a valuable platform for dissecting the molecular pathways governing mu-opioid receptor expression.
- Specific calcium channel subtypes differentially modulate mu-opioid receptor expression, suggesting targeted therapeutic potential.