Opioid-noradrenergic interactions in the neurohypophysis. I. Differential opioid receptor regulation of oxytocin, vasopressin, and noradrenaline release

• Published in: Neuroendocrinology Vol. 48; no. 1; p. 16
• Main Authors: Zhao, B G, Chapman, C, Bicknell, R J
• Format: Journal Article
• Language: English
• Published: Switzerland 1988
• Subjects: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics - pharmacology; Animals; beta-Endorphin - physiology; Electric Stimulation; Female; In Vitro Techniques; Male; Naloxone - pharmacology; Norepinephrine - secretion; Oxytocin - secretion; Pituitary Gland, Posterior - physiology; Pituitary Gland, Posterior - secretion; Pyrrolidines - pharmacology; Rats; Rats, Inbred Strains; Receptors, Opioid - physiology; Vasopressins - secretion
• ISSN: 0028-3835
• DOI: 10.1159/000124984

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.