THE OPIOID RECEPTOR SUBTYPE-MU AND SUBTYPE-KAPPA, BUT NOT DELTA, ARE INVOLVED IN THE CONTROL OF THE VASOPRESSIN AND OXYTOCIN RELEASE IN THE RAT

The effects of highly selective agonists and antagonists to the mu-, delta- and kappa-opioid receptor subtypes were studied on the vasopressin and oxytocin release in 24 h water-deprived male rats. The delta-agonist [D-Pen2,D-Pen5]enkephalin (dose range 0.01-5 mg/kg) did not affect plasma levels of either hormone 30 min after s.c. administration, whereas the mu-agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) over the same dose range strongly inhibited the release of both vasopressin and oxytocin, an effect that was maximal 30-60 min after s.c. injection. The same effect was found for s.c. administration of the kappa-agonist U-69,593. Intracerebroventricular (i.c.v.) administration of DALDA (0.5 and 5-mu-g/kg) but not U-69,593 suppressed both plasma hormone levels 30 min after injection. Also the effects of selective antagonists were tested over the s.c. dose range of 0.01-1 mg/kg. Whereas both the kappa-selective antagonist nor-binaltorphimine and the relatively mu-selective antagonist naloxone elevated oxytocin plasma levels (peak at 15 and 30 min after injection, respectively), the delta-selective antagonist naltrindole was without any effect. Nor-binaltorphimine, naloxone, and naltrindole did not affect vasopressin release. When the antagonists were administered i.c.v. (dose range 2.5-25-mu-g/kg), only the kappa-antagonist nor-binaltorphimine enhanced oxytocin and vasopressin release 30 min after injection. In conclusion, both mu- and kappa-opioid receptors are involved in the regulation of the secretion of vasopressin and oxytocin from the rat neural lobe; in contrast, delta-opioid receptors do not play a role. Furthermore, the data indicate that endogenous kappa-opioids selectively inhibit the oxytocin release although mu-agonistic opioids may also be involved.