INCREASED OPIOID BINDING TO PERIPHERAL WHITE BLOOD-CELLS IN A RAT MODEL OF ACUTE CHOLESTASIS

Background/Aims: Endogenous opioids accumulate in plasma in cholestasi s. Furthermore, immune cells have opioid receptors, and endogenous opi oids have immunomodulatory effects. This study examined the expression of opioid receptors on peripheral white blood cells in rats with acut e cholestasis after bile duct resection (BDR). Methods: Five days afte r surgery, white blood cells were isolated from peripheral blood. To d etermine total opioid binding, cells from either BDR or sham-resected rats were incubated with a fluorescently labeled opioid receptor antag onist. Specific opioid binding was determined by preincubating the cel ls with a 100-fold molar excess of unlabeled naltrexone or with one of two opioid receptor agonists: (D-Ala(2), D-Leu(5))enkephalin (delta r eceptor) or (D-Ala(2), MePhe(4), Gly-ol(5))enkephalin (mu receptor). T he proportion of neutrophils, lymphocytes, and monocytes with specific delta or mu opioid receptors was determined by flow cytometric analys is. Results: Opioid receptors on neutrophils were unaffected by BDR, w hereas the lymphocyte population of BDR rats had an increased binding to delta receptors (2.6% +/- 1.1% for sham vs. 7.3% +/- 1.4% for BDR; P < 0.02) and monocytes from BDR rats had an increased binding to mu r eceptors (7.7% +/- 0.9% for sham vs. 17.9% +/- 2.3% for BDR; P < 0.000 1). Conclusions: The selective increase of delta-receptor binding on l ymphocytes and mu-receptor binding on monocytes suggests that, in acut e cholestasis, opioid-mediated effects on white blood cell function ma y be altered.