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1 Physiology & Biophysics, University of Calgary, Calgary, Canada
* To whom correspondence should be addressed. E-mail: fsmith{at}ucalgary.ca.
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
-opioid receptor agonist, U-50488H, were measured in two separate groups of conscious lambs at two stages of postnatal maturation (~one- and ~six weeks) under physiological conditions. In order 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
-opioid receptor antagonist, 5'guanidinonaltrindole (GNTI). Urinary flow rate (V), free water clearance (CH2O), electrolyte excretions and clearances were measured for 30 min before and for 90 min after I.V. injection of U-50488H or vehicle. An increase in urinary flow rate accompanied by an increase in CH2O 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 one- or six weeks 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 pre-treatment with GNTI in both age groups. We conclude that
-opioid receptors are diuretic early in life, and that this response does not appear to be altered as post natal maturation proceeds. Therefore, these data provide evidence that activation of
-opioid receptors early in life may lead to alterations in fluid balance.
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