Diuresis and suppression of vasopressin by kappa opioids: comparison with mu and delta opioids and clonidine.
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.
Leander
J D
JD
Zerbe
R L
RL
Hart
J C
JC
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014667:Vasopressins / Q000097:blood*
D001575:Benzomorphans; D004723:Endorphins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014667:Vasopressins; D004744:Enkephalin, Methionine; D003894:Deamino Arginine Vasopressin; C027248:bremazocine; D003000:Clonidine; C028208:metkephamid