Effects of Opioid Agonists and Antagonists on Oxytocin and Vasopressin Release in vitro

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Abstract
The rat neurohypophysis contains both opioid receptors and substantial amounts of endogenous opioid peptides. Inhibitory influences of opioids on the secretion of both oxytocin and vasopressin have been described. The effects of a range of opioid agonists and antagonists with differing relative selectivities towards opioid receptor subclasses on the secretion of oxytocin and vasopressin from the isolated neurohypophysis have been examined. Oxytocin and vasopressin release evoked by brief periods of electrical stimulation in control experiments was compared to evoked release in the presence of test compounds. Oxytocin release was depressed .apprx. 25% by the .delta.-agonist (D-Ala2, D-Leu5)-enkephalin but not affected by putative .kappa.-agonists or by .beta.-endorphin. The use of opioid antagonists revealed a strong inhibition of oxytocin secretion by endogenous opioids released during electrical stimulation. Naloxone, relatively .mu.-selective, enhanced oxytocin secretion by up to 90% with a half-maximal effect at .apprx. 10-6 M. MR2266, a relatively .kappa.-selective antagonist also enhanced oxytocin secretion but displayed agonist-like activity at high concentrations. ICI 1254129, a .delta.-selective antagonist, was without effect on oxytocin secretion. Vasopressin release was unaffected by any of the agonists tested and not potentiated by antagonists at a range of stimulation frequencies. The data do not support the suggestion of an inhibitory endogenous opioid influence over vasopressin secretion within the neurohypohysis but indicate that an endogeous opioid peptide, possibly acting via .mu.- or .kappa.- rather than .delta.-receptors, strongly suppresses the secretion of oxytocin.