Effect of morphine on Na +, K + -ATPase from homogenate of synaptosomes and of synaptic membrane of rat cerebral cortex

Abstract

Effects of morphine on noradrenaline release from rat cerebrocortical synaptosomes and on the Na +, K +-ATPase activity in homogenates of synaptosomes and of synaptic membranes were examined. Both morphine (10 −3-10 −5 M) and methionine-enkephalin (M-Enk; 10 −5 M) inhibited the enhanced [ 3H]noradrenaline ([ 3H]NA) release evoked by high concentrations of K + from synaptosomes and these inhibitory actions were antagonized by naloxone (10 −4, 10 −5 M). Morphine (10 −3-10 −5 M) and M-Enk (10 −5 M) stimulated the Na +, Na +, K +-ATPase activity in homogenates of synaptosomes but not of synaptic membranes in the incubation medium containing2.2 × 10 −6–4.7 × 10 −7M free Ca 2+ and these stimulatory effects were antagonized by naloxone. In homogenates of synaptic membranes, the same concentrations of morphine and M-Enk stimulated the Na +, K +-ATPase activity suppressed by FeCl 2 (5 × 10 −7M) but not CuCl 2 nor ZnCl 2, and these stimulatory effects were antagonized by naloxone. Significant levels of Fe 2+ were liberated from synaptosomes during the preparation of synaptic membrane using distilled water. These results suggest that both morphine and M-Enk stimulate the suppressed Na +, K + -ATPase activity by interacting with Fe 2+ at opioid receptor sites, and they may play a role in the suppression of membrane depolarization and/or the release of NA through their stimulatory action on the Na +, K + -ATPase activity probably suppressed by Fe 2+ in the rat cerebral cortex.