title: Stimulus-induced depletion of pro-enkephalins, oxytocin and vasopressin and pro-enkephalin interaction with posterior pituitary hormone release in vitro.
abstract: The secretion of oxytocin (OXT) from the neurohypophysis is modulated by the actions of opioids acting via kappa-receptors. The vasopressin (AVP)-containing nerve terminals in the neurohypophysis contain the kappa-opioid agonist dynorphin, but endogenous opioid restraint of OXT secretion is observed even when AVP release is not activated, suggesting that another source of opioids is responsible for modulating OXT secretion. We now report that acute stimulation of the rat neural lobe in vivo results in depletion of the neural lobe content of OXT, AVP, dynorphin A1-17, dynorphin A1-8 and metenkephalin (Met-Enk). The dynorphin content is depleted to a similar extent as that of OXT and AVP; a correlation analysis suggests that while most dynorphin is co-secreted with AVP, a significant portion is co-secreted with OXT, consistent with a co-localisation of dynorphin with OXT. Met-Enk was depleted to a lesser extent than either hormone, consistent with a partial localisation in non-releasable pools. However, depletion of Met-Enk was also observed following naloxone-precipitated opioid withdrawal accompanying selective hypersecretion of OXT, suggesting co-secretion of OXT and Met-Enk. Met-Enk is a mu-opioid receptor agonist, but extended forms of Met-Enk, as we now report, are active at neurohypophysial kappa-receptors.
authors.affiliation: Department of Neurobiology, Babraham Institute, Cambridge, UK.
authors.forename: G
authors.initials: G
authors.lastname: Leng
authors.forename: R J
authors.initials: RJ
authors.lastname: Bicknell
authors.forename: D
authors.initials: D
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Bowden
authors.forename: C
authors.initials: C
authors.lastname: Chapman
authors.forename: J A
authors.initials: JA
authors.lastname: Russell
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation; D004744:Enkephalin, Methionine / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009021:Morphine Dependence; D009270:Naloxone / Q000494:pharmacology; D009924:Organ Culture Techniques; D010121:Oxytocin / Q000097:blood / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000502:physiology
chemical_list: D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D001127:Arginine Vasopressin; D009270:Naloxone; D010121:Oxytocin; D004744:Enkephalin, Methionine; D004399:Dynorphins; D009020:Morphine