Kappa-opioid receptors on lymphocytes of a human lymphocytic cell line: morphine-induced up-regulation as evidenced by competitive RT-PCR and indirect immunofluorescence

We have previously shown that classical brain-like kappa opioid receptors ( KOR) are constitutively expressed in lymphocytic cells, including human CEM x174 T-B hybrid cells, Jurkat -T4 cells. human peripheral blood mononuclea r cells (PBMC), human CD4(+) cells and monkey PBMC (Biochem. Biophys. Res. Commun. 209 (1995) 1003). The present study further demonstrates that the K OR of lymphocytes are activated in the presence of extracellular morphine o r U50,488H. a KOR selective agonist, and the activation causes an increase in the expression of KOR mRNA, as determined by a quantitative competitive Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) procedure. The obs erved agonist-induced KOR up-regulation was blocked by treating the cells w ith either naloxone (a KOR-partially selective antagonist) or nor-binaltorp himine (a KOR-selective antagonist). Up-regulation of lymphocytic KOR by mo rphine was also evidenced by flow cytometric analysis of phycoerythrin (PE) amplification of fluorescein isothiocyanate-conjugated arylacetamide label ing of the KOR. Although morphine binds primarily to mu-opioid receptors, t ogether with the previously reported phenomenon that morphine modulation of immune functions also exists in mit-opioid receptor knockout mice, the pre sent study confirms that opioids such as morphine may exert their effects t hrough multiple opioid receptor types and that the effects of morphine or e ndogenous opioids on immune cells could not be simply adduced from the anti cipated effects of a synthetic, selective opioid receptor ligand. (C) 2001 Elsevier Science B.V. All rights reserved.