Evaluation of endomorphin-1 on the activity of Na+ ,K+-ATPase using in vitro and in vivo studies

The goal of this study was to investigate the effects of endomorphin-1 on Na+,K+-ATPase activity in mouse brain synaptosome in vitro, and its antinociceptive interaction with the Na+,K+-ATPase inhibitor ouabain. Endomorphin-1 (0.1 nM-10 muM) produced a concentration-dependent (EC50: 43.19 nM, CI: 23.38-65.71 nM, E-max: 25.86%, CI: 24.53-27.20%), naloxone-reversible increase of the synaptosomal Na+,K+-ATPase activity. The intrathecally (i.t.) administered endomorphin-1 (2-20 mug) produced a dose-dependent short-lasting increase in the tail-flick latency. Ouabain itself (1-1000 ng, i.t.) did not cause antinociception. Treatment with 10 ng ouabain significantly decreased the antinociceptive effect of 2 mug endomorphin-1, but none of the other combinations did significantly differ from the endomorhin-1-treated groups. These data indicate that endomorphin-1 increases the activity of Na+,K+-ATPase in vitro but this effect may play a weak role in the antinociception induced by intrathecal endomorphin-1. (C) 2002 Elsevier Science B.V. All rights reserved.