Effects of opioid agonists on urine production in neonatal rats.
The modulatory effects of opioids on urine production in adult rats have been well-documented. We report here the first investigation of the effects of these agents on urination in neonatal rats. The kappa-agonists U50,488H (1,10 mg kg-1) and (+)-tifluadom (10 mg kg-1) produced an increase in urine output in 10-day old pups whereas the (-)-isomer of tifluadom was ineffective in this model. The diuretic effects of the highest dose of U50,488H were attenuated by a 10 but not a 1 mg kg-1 dose of the opioid antagonist naltrexone. These findings suggest that kappa-agonists, as in adult animals, produce diuresis in neonates by activity at kappa-opioid receptors and also confirm the stereoselective nature of the response. The increase in urination produced by U50,488H (10 mg kg-1) was also reduced by the alpha-adrenoceptor antagonist phentolamine (1 mg kg -1), an observation which supports the hypothesis that kappa-agonists--in addition to their well-established inhibitory effects on the release of antidiuretic hormone--may increase urination via an adrenergic mechanism at the level of the adrenal medulla. The mu-opioid agonist morphine (0.1-10 mg kg-1), in contrast to its observed effects in older animals, did not produce antidiuresis in either normally-hydrated or water-loaded 10-day old rat pups. The results of this study therefore show that the stimulatory effects of kappa-agonists on urine production appear to be fully-functional at 10-days but the inhibitory effects of opioids on urination lag behind in development.
Jackson
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Department of Biochemistry, University of Surrey, Guildford, UK.
Kitchen
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001569:Benzodiazepines / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014563:Urodynamics / Q000187:drug effects*
D000700:Analgesics; D009294:Narcotics; D011759:Pyrrolidines; D001569:Benzodiazepines; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C035470:tifluadom; D010646:Phentolamine