Endomorphins: Localization, release and action on rat dorsal horn neurons

Endomorphin (Endo) 1 and 2, two tetrapeptides isolated from the bovine and human brain, have been proposed to be the endogenous ligand for the mu-opia te receptor. A multi-disciplinary study was undertaken to address the issue s of localization, release and biological action of Endo with respect to th e rat dorsal horn. First, immunohistochemical studies showed that Endo-1- o r Endo-2-like immunoreactivity (Endo-1- or Endo-2-LI) is selectively expres sed in fiber-like elements occupying the superficial layers of the rat dors al horn, which also exhibit a high level of mu-opiate receptor immunoreacti vity. Second, release of immunoreactive Endo-2-like substances (irEndo) fro m the in vitro rat spinal cords upon electrical stimulation of dorsal root afferent fibers was detected by the immobilized antibody microprobe techniq ue. The site of release corresponded to laminae I and II where the highest density of Endo-2-LI fibers was localized. Lastly, whole-cell patch damp re cordings from substantia gelatinosa (SG) neurons of rat lumbar spinal cord slices revealed two distinct actions of exogenous Endo-1 and Endo-2: (1) de pression of excitatory and/or inhibitory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (2) hyperpolarization of SG neur ons. These two effects were prevented by the selective mu-opiate receptor a ntagonist beta-funaltrexamine. The localization of endomorphin-positive fib ers in superficial layers of the dorsal horn and the release of irEndo upon stimulation of dorsal root afferents together with the observation that En do inhibits the activity of SG neurons by interacting with mu-opiate recept ors provide additional support of a role of Endo as the endogenous ligand f or the mu-opiate receptor in the rat dorsal horn. Copyright (C) 2000 Nation al Science Council, ROC and S. Karger AG. Basel.