Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration.

Abstract
Sensory neurons [chicken embryo dorsal root ganglia] grown in dispersed cell culture in the absence of non-neuronal cell types contained immunoreactive substance P that was chemically similar to synthetic substance P. When depolarized in high K+ media (30-120 mM), the neurons released this peptide by a Ca2+-dependent mechanism. An enkephalin analog, [D-Ala2]enkephalin amide, at 10 .mu.M inhibited the K+-evoked release of substance P. At the same or lower concentrations, [D-Ala2]enkephalin amide and enkephalin decreased the duration of the Ca2+ action potential evoked and recorded in dorsal root ganglion cell bodies without affecting the resting membrane potential or resting membrane conductance. This modulation of voltage-sensitive channels may account for the inhibition of substance P release.