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Non-peptidic δ-opioid receptor antagonists suppress mitogen-induced tryptophan degradation in peripheral blood mononuclear cellsin vitro

Authors
Journal
Immunology Letters
0165-2478
Publisher
Elsevier
Publication Date
Volume
118
Issue
1
Identifiers
DOI: 10.1016/j.imlet.2008.03.006
Keywords
  • δ-Opioid Receptor
  • Peripheral Blood Mononuclear Cells
  • Immunosuppression
  • Indoleamine 2
  • 3-Dioxygenase
  • Tryptophan
  • Neopterin
Disciplines
  • Chemistry
  • Medicine

Abstract

Abstract Opioid receptors are expressed not only on neuroendocrine cells but also on immunocompetent cells such as lymphocytes, monocytes and macrophages. μ-Opioid receptor agonists were found to exert immunosuppressive effects, whereas δ-opioid receptor agonists have been shown to act as immunostimulants. δ-Opioid receptor agonists stimulate T and B cells and activate granulocytes and monocytes, conversely, immunostimulation can be blocked by the non-peptidic δ-opioid receptor antagonist (NTI). We investigated the impact of NTI and of the two structurally related compounds HS-378 and HS-459 on degradation of tryptophan and formation of neopterin in mitogen-stimulated human peripheral blood mononuclear cells (PBMC). Both these biochemical pathways were found to be suppressed by all three opioid receptor antagonists, HS-378 and HS-459 exhibiting slightly greater potency than NTI. The suppression of tryptophan degradation suggests that the tested δ-opioid antagonists are able to influence the serotonergic system via a non-opioid action.

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