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

摘要

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.