Effect of the opioid kappa-receptor agonist U50488H on the secretion of arginine vasopressin. Study on the mechanism of U50488H-induced diuresis.

The effect of U50488H, a potent opioid kappa-receptor agonist, was investigated on the urine volume and on the secretion of arginine vasopressin (AVP) in response to dehydration or hyperosmolar or hypovolemic stimulation in conscious rats. This agonist markedly increased the urine volume in normally hydrated rats and suppressed plasma AVP in a dose-dependent manner in rats given hyperosmolar saline. This suppression of plasma AVP was completely reversed by concurrent injection of naloxone. U50488H also inhibited the release of AVP in dehydrated or hypovolemic rats. These findings indicate that the diuresis induced by U50488H is mainly caused by the suppression of plasma AVP. They also suggest that the kappa-opioid receptor plays an important role in regulating the secretion of AVP.