The opioid receptor subtypes mu and 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 micrograms/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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Van de Heijning
B J
BJ
Department of Medical Pharmacology, University of Utrecht, The Netherlands.
Koekkoek-Van den Herik
I
I
Van Wimersma Greidanus
T B
TB
D000818:Animals; D008297:Male; D009292:Narcotic Antagonists; D010121:Oxytocin / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014667:Vasopressins / Q000097:blood / Q000378:metabolism*
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014667:Vasopressins; D010121:Oxytocin