mu-Opioid receptor gene expression: the role of NCAM.
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.
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Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455-0217, USA.
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D000818:Animals; D001095:Arachidonic Acids; D020746:Calcium Channels, L-Type / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002449:Cell Aggregation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D001095:Arachidonic Acids; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D019006:Neural Cell Adhesion Molecules; D017450:Receptors, Opioid, mu; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases; D005968:Glutamate Decarboxylase