Abstract
Opioids and cannabinoids modulate T lymphocyte functions. Many effects of the drugs are mediated by μ-opioid receptor and cannabinoid receptor type 1 (CB1), respectively. These two receptors are strikingly similar with respect to their expression in T cells and the mechanisms by which they mediate modulation of T cell activity. Thus, μ-opioid receptors and CB1 not expressed in resting primary human and Jurkat T cells. However, in response to the cytokine IL-4, the epigenetic modifiers 5-aza-2'-deoxycytidine and trichostatin A, and activation of T cells, functional μ-opioid receptors and CB1 are induced. The induced receptors mediate inhibition of T cell signaling and, thereby, IL-2 production, a hallmark of activated T cells. Although coupled to inhibitory G proteins, μ-opioid receptors and CB1 produce a remarkable increase in cAMP levels in T cells stimulated with opioids and cannabinoids, which is a key mechanism for the inhibition of T cell signaling.
© 2012 New York Academy of Sciences.
MeSH terms
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Analgesics, Opioid / immunology
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Analgesics, Opioid / pharmacology
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Animals
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Azacitidine / analogs & derivatives
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Azacitidine / pharmacology
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Cannabinoids / immunology
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Cannabinoids / pharmacology
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Cyclic AMP / immunology
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Cyclic AMP / metabolism
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Decitabine
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Humans
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Hydroxamic Acids / pharmacology
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / immunology
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Interleukin-4 / immunology
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Interleukin-4 / metabolism*
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Jurkat Cells
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Mice
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Neuroimmunomodulation*
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Receptor, Cannabinoid, CB1 / immunology
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Receptor, Cannabinoid, CB1 / metabolism*
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Receptors, Opioid, mu / immunology
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Receptors, Opioid, mu / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / immunology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
Substances
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Analgesics, Opioid
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Cannabinoids
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Hydroxamic Acids
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Interleukin-2
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Receptor, Cannabinoid, CB1
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Receptors, Opioid, mu
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Interleukin-4
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trichostatin A
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Decitabine
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Cyclic AMP
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Azacitidine