Opioid receptors on cells of the immune system: evidence for δ- and κ-classes

Abstract

Opioid peptides have been shown to modulate various parameters of both the humoral and cellular arms of the immune system. The modulatory capacity of the peptides can often be substantially reduced in the presence of naloxone, an opioid receptor antagonist, indicating a classical ligand-receptor interaction. In order to characterize these interactions further, we investigated the characteristics of opioid receptors on a macrophage cell line, P388d1. A delta-class opioid receptor was found with an Mr of 58,000. We also identified opioid receptors on MOLT-4 (T-cell) and IM-9 (B cell) cell lines as well as thymocytes and T cell-and B cell-enriched populations. Using the central (brain) kappa-selective agonist, U-69,593, it was also determined that P388d1 cells possess kappa-like opioid receptors. Scatchard analysis of the binding of [3H]U-69,593 revealed a single population of sites with a dissociation constant of 17 +/- 3 (S.E.M.) nmol/l and a total number of binding sites of 53.8 +/- 1.0 (S.E.M.) fmol/10(6) cells. Moreover, the racemic kappa-selective agonist U-50,488H was able to displace 50% of [3H]U-69,593 binding at 8.0 nmol/l, whereas other opioid ligands such as [Met]-enkephalinamide (delta-selective) and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (mu-selective) were ineffective displacers of [3H]U-69,593 except at high concentrations.

Morphine Enhances HIV Infection of Neonatal Macrophages

“…Evidence for the expression of opiate receptors on immune cells, in particular receptors for morphine and the metabolites of heroin, provided a biologic link between opiates and the cells of the human immune system (25,26). Opioid receptors (, , and ␦), as well as nonclassic opioidlike receptors, are present on cells of the human immune system (27)(28)(29)(30). Binding sites for the novel morphine receptor designated 3 are detectable on human peripheral blood isolated monocytes (31).…”

Immunofluorescence Detection of δ Opioid Receptors (DOR) on Human Peripheral Blood CD4+ T Cells and DOR-Dependent Suppression of HIV-1 Expression

“…SNC-80 significantly suppressed p24 Ag expression by both strains of HIV-1. In several species, mononuclear cells contain DOR transcripts, although very few studies have provided substantial evidence for the detection of DOR itself (19,20). DOR transcript levels are uniformly low in freshly obtained mononuclear cells, requiring reverse transcription with PCR and a relatively large number of amplification cycles for detection in simian and human PBMC and in murine splenocytes (8 -11).…”

The immune system as the sixth sense

“…In large measure, opioid receptors are of the l, or d class and each class can be found on immune cells. Specifically, using a d class-selective ligand ([ 3 H]cis-(+)-3-methyl-fentanyl-isothiocyanate), a binding site with a molecular weight of 58 kDa was specifically labelled on murine lymphocytes [30] and the P388d 1 macrophage cell line [31]. The l-selective, site-directed acylating agent,…”