Dynorphin A inhibits and naloxone increases the electrically stimulated release of oxytocin but not vasopressin from the terminals of the neural lobe.
Oxytocin release from the rat neurohypophysis is under endogenous opioid inhibition. It has recently been established that dynorphin precursor-derived peptides are colocalized with vasopressin (VP) in the secretory granules in nerve terminals of the neural lobe, and that the opiate receptors in the neural lobe are restricted to the kappa-subtype. Therefore, we hypothesized that dynorphin, which is copackaged and thus coreleased with VP, is the endogenous opioid that inhibits release from neighboring oxytocin (OT) terminals. To test this hypothesis we examined the effects of dynorphin-(1-8), dynorphin-(1-17), and naloxone on the electrically stimulated release of OT and VP from isolated rat neurointermediate lobes throughout a range of stimulus frequencies. Both dynorphin-(1-8) and -(1-17) (2 microM) produced a substantial reduction in OT release during a 4-Hz stimulus, and this effect was abolished by naloxone (10 microM). Neither form of dynorphin, however, affected OT secretion at a stimulus frequency of 12 or 30 Hz at concentrations up to 10 microM. Naloxone (10 microM) by itself did not affect OT release during the 4-Hz stimulus, but it produced a substantial increase in OT release at a stimulus frequency of 12 Hz. In contrast, neither form of dynorphin produced inhibition, nor did naloxone augment VP secretion at any frequency tested. Frequency-dependent secretion curves (4, 8, 12, 20, and 30 Hz) for OT and VP in the presence and absence of naloxone indicated that the degree of naloxone augmentation of OT release at a given stimulus frequency was positively correlated with the amount of VP release at that frequency. These data support the hypothesis that dynorphin released in parallel with VP during in vitro stimulations of the rat neurohypophysis simultaneously inhibits stimulated OT release.
D000818:Animals; D004399:Dynorphins / Q000494:pharmacology*; D004558:Electric Stimulation; D008297:Male; D008954:Models, Biological; D009270:Naloxone / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology*
D010446:Peptide Fragments; D014667:Vasopressins; D009270:Naloxone; D010121:Oxytocin; D004399:Dynorphins; C026770:dynorphin (1-8)