Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioids and cannabinoids are both associated with analgetic, psychotropic, and immunomodulatory effects. It has been suggested that both systems interact on multiple levels. We hypothesized that cannabinoids induce opioid receptors and investigated cannabinoid-dependent expression of the mu-opioid receptor subtype in a human T cell model. We report that activation of the peripheral cannabinoid receptor type 2 leads to a de novo induction of mu-opioid receptor transcription in Jurkat E6.1 cells. We show that interleukin-4 is transcriptionally induced in response to cannabinoids and that an interleukin-4 receptor antagonist blocks cannabinoid-dependent induction of mu-opioid receptors, indicating that induced expression of interleukin-4 is required in this process. Induction of interleukin-4 is blocked by decoy oligonucleotides directed against STAT5, indicating the requirement of this transcription factor. In addition, we show cannabinoid-dependent phosphorylation of STAT5. Further experiments demonstrate that interleukin-4 then induces phosphorylation of STAT6, which directly transactivates the mu-opioid receptor gene. In addition, STAT6 induces expression of the transcription factor GATA3, which also contributes to mu-opioid receptor gene transcription. The responsive promoter region of the human mu-opioid receptor gene with the binding sites for both factors was mapped to nt -1001 to -950. To demonstrate functional mu-opioid receptor proteins, morphine-mediated phosphorylation of mitogen-activated protein kinase was investigated. We show that phosphorylation of mitogen-activated protein kinase occurs only in cannabinoid-prestimulated Jurkat E6.1 cells and that it is blocked by the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. In summary, these findings provide a first example for cannabinoid-opioid-interactions in cells of the immune system.
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PMID:Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. 1643 16

Compared with control rats, rats under morphine exposure exhibited cannabinoid receptor 2 (CB2-R) upregulation in the spleen and periphery blood mononuclear cells (PBMCs). IgG and IgM values in the plasma were also altered. In morphine abusers, cannabinoid receptors were upregulated in the PBMCs, and the expression of IL-4 mRNA in the PBMCs as well as the IgG and IgM values in the plasma were higher compared with those in healthy people. The expression of cannabinoid receptor 1 and CB2-R in culture cells was directly affected by morphine treatment. These findings indicate that the alteration in cannabinoid receptor expression could be disturbed by morphine exposure, and it may be involved in abnormal immune function.
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PMID:Exposure to morphine affects the expression of endocannabinoid receptors and immune functions. 2254 45