title: Opioid-noradrenergic interactions in the neurohypophysis. I. Differential opioid receptor regulation of oxytocin, vasopressin, and noradrenaline release.
abstract: The actions of opioids on electrically evoked release of oxytocin, vasopressin, and noradrenaline-using the [3H]-noradrenaline technique-from the rat neurohypophysis were examined in vitro. Antagonism of the action of endogenous neurohypophysial opioids with naloxone enhanced release of peptides and [3H]-noradrenaline differentially. Naloxone enhanced oxytocin release by 100 and 173% in two series of experiments (ED50 7 x 10(-7) M), whilst vasopressin release was enhanced by only 30 and 20%, respectively. [3H]-noradrenaline release was maximally enhanced by 41% (ED50 2 x 10(-7) M). We examined the opioid receptor subtypes mediating these effects using selective receptor agonists. The kappa-agonist U-50,488H inhibited oxytocin and vasopressin release to a similar extent, but did not modify [3H]-noradrenaline release. The effects of U-50,488H were completely prevented by a tenfold molar excess of naloxone. The mu-agonist (D-Ala2, MePhe5 Gly-ol)-enkephalin also failed to inhibit [3H]-noradrenaline release and caused only a minor inhibition of oxytocin and vasopressin secretion. The delta-agonist (D-Pen2, D-Pen5)-enkephalin was without effect. We conclude that (1) kappa-receptors sensitive to U-50,488H mediate opioid inhibition of secretion from oxytocin and vasopressin nerve terminals; (2) when opioid actions are blocked by naloxone, opioid peptides within the neurohypophysis are shown to exert a much greater influence over oxytocin compared to vasopressin terminals; (3) neurohypophysial opioids also regulate release from noradrenergic terminals, although the nature of the receptors involved remains unclear, and (4) kappa-receptors can mediate inhibition of neurohormone secretion by an action independent of the neurohypophysial noradrenergic innervation.
authors.affiliation: Department of Neuroendocrinology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, UK.
authors.forename: B G
authors.initials: BG
authors.lastname: Zhao
authors.forename: C
authors.initials: C
authors.lastname: Chapman
authors.forename: R J
authors.initials: RJ
authors.lastname: Bicknell
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000378:metabolism* / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism*; D001615:beta-Endorphin / Q000502:physiology*
chemical_list: D000700:Analgesics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D014667:Vasopressins; D009270:Naloxone; D010121:Oxytocin; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009638:Norepinephrine