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 differential-opioid receptor agonists on K(+)-evoked [Met(5)]-enkephalin release from superfused rat spinal cord slices. 1DMe (0.1-10 microM) dose-dependently enhanced the increase in superfusate [Met(5)]-enkephalin content due to the peptidase inhibitors thiorphan (1 microM) and bestatin (20 microM), and prevented the reduction in [Met(5)]-enkephalin release due to stimulation of partial differential receptors by 1 microM deltorphin I. Because it had the same effects as partial differential-opioid receptor antagonists, 1DMe might act through the functional blockade of presynaptically located partial differential-opioid autoreceptors.