Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 160 (2), 229-37

Mechanism of Diuretic Action of U-62,066E, a Kappa Opioid Receptor Agonist

Affiliations

Mechanism of Diuretic Action of U-62,066E, a Kappa Opioid Receptor Agonist

K Yamada et al. Eur J Pharmacol.

Abstract

The mechanism of the diuretic action of U-62,066E, a highly selective kappa opioid agonist, was examined in unanesthetized rats and in isolated perfused inner medullary collecting ducts (IMCD). In Long-Evans rats, U-62,066E caused a dose-dependent increase in urine flow and a decrease in urine osmolality without affecting urinary excretion of Na+. The diuretic effect of U-62,066E was blocked by MR-2266, a kappa opioid receptor antagonist. U-62,066E showed no diuretic effect in homozygous hereditary diabetes insipidus rats (Brattleboro strain). In water-deprived rats, U-62,066E markedly inhibited plasma arginine vasopressin (AVP) levels through a kappa receptor-mediated mechanism. In rat IMCD perfused in vitro, 10(-5) M U-62,066E did not inhibit either the baseline or the AVP-stimulated osmotic water permeability. We conclude that the inhibition of the release of AVP is the major if not the entire mechanism of the diuretic action of U-62,066E in rats. Although we ruled out the effect of this drug on the water permeability of IMCD, possible direct effects on other nephron structures remain to be established.

Similar articles

See all similar articles

Cited by 7 PubMed Central articles

See all "Cited by" articles

LinkOut - more resources

Feedback