STIMULUS-INDUCED DEPLETION OF PRO-ENKEPHALINS, OXYTOCIN AND VASOPRESSIN AND PROENKEPHALIN INTERACTION WITH POSTERIOR PITUITARY-HORMONE RELEASE IN-VITRO

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 ka ppa-opioid agonist dynorphin, but endogenous opioid restraint of OXT s ecretion is observed even when AVP release is not activated, suggestin g that another source of opioids is responsible for modulating OXT sec retion. We now report that acute stimulation of the rat neural lobe in vivo results in depletion of the neural lobe content of OXT, AVP, dyn orphin A(1-17), dynorphin A(1-8) and metenkephalin (Met-Enk). The dyno rphin content is depleted to a similar extent as that of OXT and AVP; a correlation analysis suggests that while most dynorphin is co-secret ed 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 locali sation in non-releasable pools. However, depletion of Met-Enk was also observed following naloxone-precipitated opioid withdrawal accompanyi ng 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-rec eptors.