A kappa opioid effect: increased urination in the rat.

The effects of various opioids (mu agonists, kappa agonists and mixed agonists/antagonists) were determined on urination in the normally dehydrated 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 the kappa agonists, but more than the mu agonists (morphine and l-methadone). The mu agonists did not increase urine output 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. The data suggest the hypothesis that dynorphin, a kappa agonist, acts 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.