Possible involvement of membrane phospholipids in inhibition by ferrous ions of [3H]MK-801 binding to the native N-methyl-D-aspartate channel in rat brain.
Prior treatment with ferrous chloride led to the marked inhibition of [3H](+)-5-methyl-10, 11-dihydro-5H-dibenzo[a, d]cyclohepten-5, 10-imine (MK-801) binding to an open ion channel associated with the N-methyl-D-aspartate (NMDA) receptor in a concentration-dependent manner at concentrations of higher than 1 microM in rat brain synaptic membranes. Both phospholipases A2 and C significantly prevented the inhibition when treated before the treatment with ferrous chloride, while neither superoxide dismutase nor alpha-tocopherol affected the inhibition even when treated simultaneously with ferrous chloride. Of various saturated and unsaturated fatty acids, moreover, both oleic and arachidonic acids exclusively decreased the potency of ferrous chloride to inhibit binding when membranes were treated with fatty acids, followed by a second treatment with ferrous chloride. These results suggest that membrane phospholipids may be, at least in part, responsible for the interference by ferrous ions in the opening processes of the native NMDA channel through molecular mechanisms associated with the release of unsaturated fatty acids in rat brain.
Yoneda
Y
Y
Department of Pharmacology, Setsunan University, Osaka, Japan.
Ogita
K
K
Shuto
M
M
Manabe
T
T
Kitayama
T
T
D000818:Animals; D001921:Brain / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology*; D008297:Male; D008563:Membrane Lipids / Q000502:physiology*; D010740:Phospholipases / Q000494:pharmacology; D010743:Phospholipids / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013570:Synaptic Membranes / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D005227:Fatty Acids; D005296:Ferrous Compounds; D007473:Ion Channels; D008563:Membrane Lipids; D010743:Phospholipids; D016194:Receptors, N-Methyl-D-Aspartate; D014810:Vitamin E; D016291:Dizocilpine Maleate; D007501:Iron; D013482:Superoxide Dismutase; D010740:Phospholipases; C029451:ferrous chloride