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JD Leander, RL Zerbe and JC Hart
The effects of agonists at kappa, mu and delta opioid receptors were determined on vasopressin levels in water-deprived rats. Bremazocine and U-50, 488 (kappa agonists) markedly suppressed vasopressin levels, whereas morphine and methadone (mu agonists) and metkephamid (a mixed mu and delta agonist) did not suppress vasopressin levels. Likewise, clonidine, a potent diuretic in normally hydrated rats, did not clearly suppress vasopressin levels. Metkephamid was shown to have a modest diuretic effect in normally hydrated rats but not in water-deprived rats. The diuretic effects of bremazocine were blocked completely by simultaneous treatment with desmopressin, a synthetic vasopressin-like analog. Desmopressin also blocked the diuretic effect of a waterload, but only partially attenuated the diuretic effect of clonidine. These results support the hypothesis that kappa opioid agonists produce a diuretic effect by suppressing plasma levels of vasopressin, and at higher doses produce a pattern of urination similar to animals lacking vasopressin. By comparison, mu and delta opioid agonists have little effect on vasopressin levels in water-deprived rats.
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