Abstract
The effects on oxytocin release of enkephalin analogues, thought to be highly selective agonists of the μ or δ opioid receptor, were compared. Oxytocin release was evoked in urethane-anaesthetised rats (7–10 days post partum) by intracerebroventricular injection of NaCl (3M) at 15–20 min. intervals and detected by the resultant increase in intramammary pressure. Enkephalin analogues (the μ receptor agonist Tyr-D-Ala-Gly-MePhe-NH (CH 2) 2OH (DAGO), the ° receptor agonist (D-Ala 2-D-Leu 5) - enkephalin (DADLE) and metkephamid, which has been reported to be particularly efficacious at the δ receptor) were administered intracerebroventricularly 3–5 min. prior to hypertonic saline. Oxytocin release was inhibited in a dose-dependent, naloxone-reversable manner by DAGO (ED 50 : 40ng), DADLE (ED 50 : 156ng) and metkephamid (ED 50 : 42ng); the mammary gland sensitivity to oxytocin was unaffected. These results suggest that the inhibitory action may be mediated through both μ and δ receptors and provide further evidence in support of a role of enkephalins in the control of oxytocin secretion.
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