The neuropeptide FF analogue, 1DMe, acts as a functional opioid autoreceptor antagonist in the rat spinal cord

We assessed the possible influence of a neuropeptide FF analogue, 1DMe ([D-Tyr(1),(NMe)Phe(3)]neuropeptide FF), on the inhibitory action of endogenous and exogenous partial derivative -opioid receptor agonists on K+-evoked [Met(5)]-enkephalin release from superfused rat spinal cord slices. 1DMe (0.1-10 muM) dose-dependently enhanced the increase in superfusate [Met(5)]-enkephalin content due to the peptidase inhibitors thiorphan (1 muM) and bestatin (20 muM), and prevented the reduction in [Met5]-enkephalin release due to stimulation of partial derivative receptors by 1 muM deltorphin 1. Because it had the same effects as partial derivative -opioid receptor antagonists, 1DMe might act through the functional blockade of presynaptically located partial derivative -opioid autoreceptors. (C) 2001 Elsevier Science BY. All rights reserved.