Central regulation of urine production by a selective mu-opioid agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, in rats.

We have investigated opioid mechanisms concerning regulation of urine production in the hypothalamic supraoptic nucleus (SON). In this study, the effect of [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), a potent selective mu-opioid agonist, microinjected into the SON of anesthetized hydrated rats, on the urine outflow rate was examined. DAMGO caused a dose-dependent decrease in the urine outflow rate with no significant changes in blood pressure nor heart rate. The ED50 value for the antidiuresis was calculated to be 0.055 nmol from the dose-response curve. The antidiuresis elicited by DAMGO (0.1 nmol) was partially inhibited by intra-SON pre-injection of naloxone (3 nmol), a relatively mu-selective opioid antagonist, and timolol (100 nmol), a beta-adrenoceptor antagonist, but not by intra-SON pre-injection of phenoxybenzamine (20 nmol), an alpha-adrenoceptor antagonist, nor atropine (300 nmol), a muscarinic antagonist. Intravenous injection of d(CH2)5-D-Tyr(Et)VAVP (16.7 micrograms), a vasopressin receptor antagonist, did not influence the DAMGO-induced antidiuresis. These findings suggest that antidiuresis mediated through mu-opioid receptors in the SON involves beta-adrenoceptors in the nuclei, but does not involve an increase in vasopressin release.