Effect of morphine on Na+,K(+)-ATPase from homogenate of synaptosomes and of synaptic membrane of rat cerebral cortex.
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+,K(+)-ATPase activity in homogenates of synaptosomes but not of synaptic membranes in the incubation medium containing 2.2 X 10(-6)-4.7 X 10(-7) M free Ca2+ 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 FeCl2 (5 X 10(-7) M) but not by CuCl2 nor ZnCl2, and these stimulatory effects were antagonized by naloxone. Significant levels of Fe2+ 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 Fe2+ 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 Fe2+ in the rat cerebral cortex.
Nishikawa
T
T
Department of Pharmacology, Kagoshima University Dental School, Japan.
Teramoto
T
T
Shimizu
S
S
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000201:enzymology*; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology*
D004744:Enkephalin, Methionine; D009020:Morphine; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine