Met-enkephalin inhibits 5-hydroxytryptamine release from the rat ventral spinal cord via δ opioid receptors

Abstract

The effect of opioid receptor agonists and antagonists on the electrically evoked release of endogenous serotonin (5-hydroxytryptamine, 5-HT) was studied in superfused slices of the rat ventral lumbar spinal cord. Met-ENK (1 × 10−8M−1 × 10−6M) and DPDPE (1 × 10−8M−1 × 10−6M) reduced the evoked 5-HT release in a concentration dependent fashion. DAMGO (1 × 10−8−1 × 10−6M) and (−)-trans-(1S,2S)-U-50488 (1 × 10−6M) had no effect on the 5-HT release. The inhibitory effect of met-ENK was completely abolished by ICI-174,864, but neither by naloxonazine nor nor-binaltorphimine. Following i.c.v. treatment with 5,7-dihydroxytryptamine (5,7-DHT), the tissue concentration of 5-HT was reduced by 97%, whereas the concentration of noradrenaline was reduced by only 5%. The tissue concentration of met-ENK, as measured by radioimmunoassay, was not significantly altered. The results suggest that met-ENK is present in the rat ventral spinal cord mainly in non-serotonergic nerve terminals and exerts an inhibitory action on 5-HT release via δ opioid receptors.