title: Renal responses to the kappa-opioid-receptor agonist U-50488H in conscious lambs.
abstract: In adult animals and humans, activation of kappa-opioid receptors results in a diuresis. The aim of the present study was to investigate whether kappa-opioids are also diuretic early in life and whether this is altered during postnatal maturation. Therefore, the renal effects of the kappa-opioid-receptor agonist U-50488H were measured in two separate age groups of conscious lambs at two stages of postnatal maturation (approximately 1 wk and approximately 6 wk) under physiological conditions. To evaluate whether the renal responses to U-50488H resulted from receptor-dependent effects, responses to U-50488H were also tested in the presence of the specific kappa-opioid-receptor antagonist 5'-guanidinonaltrindole (GNTI). Urinary flow rate, free water clearance, and electrolyte excretions and clearances were measured for 30 min before and for 90 min after intravenous injection of U-50488H or vehicle. An increase in urinary flow rate accompanied by an increase in free water clearance occurred in response to administration of U-50488H but not vehicle. There were no effects of U-50488H on electrolyte excretions or clearances at either 1 or 6 wk of postnatal life. Although there were no effects of GNTI on any of the measured or calculated variables, the aforementioned diuretic response to U-50488H was abolished by pretreatment with GNTI in both age groups. We conclude that kappa-opioid receptors are diuretic early in life and that this response does not appear to be altered as postnatal maturation proceeds. Therefore, these data provide evidence that activation of kappa-opioid receptors early in life may lead to alterations in fluid balance.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
authors.forename: K Kumar
authors.initials: KK
authors.lastname: Ebenezar
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Samhan
authors.forename: Francine G
authors.initials: FG
authors.lastname: Smith
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000652:urine; D006146:Guanidines / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000254:growth & development; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D012756:Sheep; D014563:Urodynamics / Q000502:physiology
chemical_list: C503316:6'-guanidinonaltrindole; D018712:Analgesics, Non-Narcotic; D004573:Electrolytes; D006146:Guanidines; D017473:Receptors, Opioid, kappa; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer