title: Non-peptidic delta-opioid receptor antagonists suppress mitogen-induced tryptophan degradation in peripheral blood mononuclear cells in vitro.
abstract: Opioid receptors are expressed not only on neuroendocrine cells but also on immunocompetent cells such as lymphocytes, monocytes and macrophages. micro-Opioid receptor agonists were found to exert immunosuppressive effects, whereas delta-opioid receptor agonists have been shown to act as immunostimulants. delta-Opioid receptor agonists stimulate T and B cells and activate granulocytes and monocytes, conversely, immunostimulation can be blocked by the non-peptidic delta-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 delta-opioid antagonists are able to influence the serotonergic system via a non-opioid action.
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Marcel
authors.initials: M
authors.lastname: Jenny
authors.forename: Christiana
authors.initials: C
authors.lastname: Winkler
authors.forename: Mariana
authors.initials: M
authors.lastname: Spetea
authors.forename: Harald
authors.initials: H
authors.lastname: Schennach
authors.forename: Helmut
authors.initials: H
authors.lastname: Schmidhammer
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007737:Kynurenine / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000378:metabolism
chemical_list: D010455:Peptides; D017465:Receptors, Opioid, delta; D007737:Kynurenine; D014364:Tryptophan