Expression and functions of μ-opioid receptors and cannabinoid receptors type 1 in T lymphocytes

Ann N Y Acad Sci. 2012 Jul:1261:1-6. doi: 10.1111/j.1749-6632.2012.06524.x.

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.

MeSH terms

  • Analgesics, Opioid / immunology
  • Analgesics, Opioid / pharmacology
  • Animals
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Cannabinoids / immunology
  • Cannabinoids / pharmacology
  • Cyclic AMP / immunology
  • Cyclic AMP / metabolism
  • Decitabine
  • Humans
  • Hydroxamic Acids / pharmacology
  • Interleukin-2 / antagonists & inhibitors
  • Interleukin-2 / immunology
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism*
  • Jurkat Cells
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Neuroimmunomodulation*
  • Receptor, Cannabinoid, CB1 / immunology
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptors, Opioid, mu / immunology
  • Receptors, Opioid, mu / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Analgesics, Opioid
  • Cannabinoids
  • Hydroxamic Acids
  • Interleukin-2
  • Receptor, Cannabinoid, CB1
  • Receptors, Opioid, mu
  • Interleukin-4
  • trichostatin A
  • Decitabine
  • Cyclic AMP
  • Azacitidine