STUDIES ON THE NATURE AND MECHANISM OF THE DIURETIC ACTIVITY OF THE OPIOID ANALGESIC ETHYLKETOCYCLAZOCINE

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 220  (3) , 585-591
Abstract
S.c. injection (0.1-3.0 mg/kg) of ethylketocyclazocline (EKC; a prototype kappa agonist) resulted in a dose-dependent increase in urine formation in conscious rats. The increase in urine volume was unaccompanied by a corresponding increase in electrolyte excretion; EKC behaved like a water diuretic. The diu-etic activity was completely abolished by naltrexone, an opiate antagonist. H2O loading (10 ml/kg) diminished plasma vasopressin levels equally 60 min after treatment. Urine formation during the 1st h was greater in EKC-treated rats than in H2O-loaded rats. Evidently, more than 1 component was responsible for the diuretic activity of EKC. A central effect of EKC on plasma vasopressin and urine volume was not evident. EKC (10 .mu.g/rat) when injected s.c. caused diuresis, but was ineffective as a diuretic when injected into the lateral ventricle. EKC was effective in blocking stimulation of vasopressin secretion caused by volume contraction. EKC also blocked vasopressin-stimulated H2O flow in the toad bladder, a model of the renal distal tubule and collecting duct. Apparently, EKC is diuretic by virtue of inhibition of vasopressin secretion and attenuation of the vasopressin response in the kidney. Both of these actions may be mediated by opioid receptors responsive to kappa agonists and inaccessible from the cerebroventricle.