• Leon F Tseng.
• Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA. ltseng@mcw.edu
• Jpn. J. Pharmacol. 2002 Jul 1;89(3):216-20.

AbstractTwo highly selective mu-opioid receptor agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), have been identified and postulated to be endogenous mu-opioid receptor ligands. The present minireview describes the antinociceptive properties with the tail-flick test of these two ligands given intracerebroventricularly (i.c.v.) and intrathecally (i.t.) in ICR mice. EM-1 or EM-2 given i.c.v. or i.t. dose-dependently produce antinociception. These antinociceptive effects induced by EM-1 and EM-2 given i.c.v. or i.t. are selectively mediated by the stimulation of mu-, but not delta- or kappa-opioid receptors. Like other mu-opioid agonists morphine and DAMGO ([D-Ala2,NMePhe4,Gly5-ol]enkephalin), EM-1 and EM-2 given i.c.v. activate descending pain controls by the releases of noradrenaline and 5-HT and subsequently act on alpha2-adrenoceptors and 5-HT receptors, respectively, in the spinal cord to produce antinociception. However, the antinociception induced by EM-2 given i.c.v. or i.t. also contain an additional component, which is mediated by the release of dynorphin A(1-17) acting on kappa-opioid receptors at the supraspinal and spinal sites. In addition, the antinociception induced by EM-2 given i.c.v. contains another component, which is mediated by the release of Met-enkephalin acting on delta2-opioid receptors in the spinal cord. It is proposed that there are two subtypes of mu-opioid receptors,which are involved in EM-1- and EM-2-induced antinociception. One subtype of mu-opioid receptors is stimulated by EM-1, EM-2 and other mu-opioid agonists morphine and DAMGO; and another subtype of mu-opioid is sorely stimulated by EM-2 and is involved in the releases of dynorphin A(1-17) and Met-enkephalin for the production of antinociception.

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