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Inhibition of oxytocin secretion by mu and delta receptor selective enkephalin analogues
Abstract:
The effects on oxytocin release of enkephalin analogues, thought to be highly selective agonists of the mu or delta 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 mu receptor agonist Tyr-D-Ala-Gly-MePhe-NH (CH2)2OH (DAGO), the delta receptor agonist (D-Ala2-D-Leu5) - enkephalin (DADLE) and metkephamid, which has been reported to be particularly efficacious at the delta receptor) were administered intracerebroventricularly 3-5 min. prior to hypertonic saline. Oxytocin release was inhibited in a dose-dependent, naloxone-reversable manner by DAGO (ED50 : 40ng), DADLE (ED50 : 156ng) and metkephamid (ED50 : 42ng); the mammary gland sensitivity to oxytocin was unaffected. These results suggest that the inhibitory action may be mediated through both mu and delta receptors and provide further evidence in support of a role of enkephalins in the control of oxytocin secretion.
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