A KAPPA-OPIOID EFFECT - INCREASED URINATION IN THE RAT

Abstract

The effects of various opioids (.mu.-agonists, .kappa.-agonists and mixed agonists/antagonists) were determined on urination in the normally hydrated rat. Opioids considered as .kappa.-agonists (bremazocine, ethylketazocine and ketazocine) produced a marked dose-related increase in urination. The mixed agonists/antagonists (cyclazocine, butorphanol and nalorphine) produced less urination than did the .kappa.-agonists, but more than the .mu.-agonists (morphine and l-methadone). The .mu.-agonists did not increase urine output as compared with controls. The increased urination effect was blocked by opioid antagonists in a potency order which indicated that the effect was due to an action at a .kappa.-opioid receptor. Dynorphin, a .kappa.-agonist, may act as an endogenous ligand for an autoreceptor which inhibits the corelease of dynorphin and antidiuretic hormone from the neurohypophysis. This decrease in antidiuretic hormone levels produces the increased urination. Increased urination is a simple in vivo test for studying the actions of compounds at .kappa.-opioid receptors.