Renal effects of BW373U86 are mediated by delta opioid receptors

In previous studies, we have demonstrated that intravenous (i.V.) infusion of BW373U86 (BW), a non-peptide opioid agonist, produced a significant increase in urine flow rate (V) and urinary sodium excretion (U_MV). To characterize the subtype(s) of the opioid receptor(s) that mediates the renal effects of BW, we examined the renal responses produced by BW infusion in conscious Sprague-Dawley rats (n=5), or in rats pretreated with naltrindole (n=7), a selective delta opioid receptor antagonist. Rats were chronically instrumented with femoral arterial and venous catheters and a bladder cannula for collection of urine samples. During continuous isotonic saline infusion (55 μl/min, i.v.), changes in V and U_NaV were measured during control (20 min) and during six consecutive experimental periods (10 min ea) after the start of BW infusion (50 μg/kg/min, i.v.). Renal responses to BW infusion were also examined in rats pre-treated with naltrindole (1 mg/kg, i.v.). Results: BW produced a significant increase in V (22.5±3.5 to 54.2±4.8 μl/min/gKw) and U_NaV (4.0±0.6 to 5.9±0.6 μeq/min/gKw) 30 min after the start of infusion. In contrast, in rats pretreated with naltrindole, BW did not alter V or U_NaV throughout the protocol. In other studies, naltrindole pretreatment did not alter the renal responses produced by the kappa or mu-opioid agonists, U-50488H (20 μg/kg/min, i.v.) or dermorphin (0.3 mg/kg, i.V.), resp. These results demonstrate that the diuretic and natriuretic responses produced by BW are mediated via a pathway involving delta opioid receptors since the renal responses produced by this opioid are abolished by naltrindole.