Increased opioid binding to peripheral white blood cells in a rat model of acute cholestasis.

Abstract

Endogenous opioids accumulate in plasma in cholestasis. Furthermore, immune cells have opioid receptors, and endogenous opioids have immunomodulatory effects. This study examined the expression of opioid receptors on peripheral white blood cells in rats with acute cholestasis after bile duct resection (BDR). Five days after surgery, white blood cells were isolated from peripheral blood. To determine total opioid binding, cells from either BDR or sham-resected rats were incubated with a fluorescently labeled opioid receptor antagonist. Specific opioid binding was determined by preincubating the cells with a 100-fold molar excess of unlabeled naltrexone or with one of two opioid receptor agonists: (D-Ala2, D-Leu5)-enkephalin (delta receptor) or (D-Ala2, MePhe4, Gly-ol5)enkephalin (mu receptor). The proportion of neutrophils, lymphocytes, and monocytes with specific delta or mu opioid receptors was determined by flow cytometric analysis. Opioid receptors on neutrophils were unaffected by BDR, whereas 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 receptors (7.7% +/- 0.9% for sham vs. 17.9% +/- 2.3% for BDR; P < 0.0001). The selective increase of delta-receptor binding on lymphocytes and mu-receptor binding on monocytes suggests that, in acute cholestasis, opioid-mediated effects on white blood cell function may be altered.