Potentiation by calcium ions of [3H]MK-801 binding to an ion channel associated with the N-methyl-D-aspartate receptor complex in rat brain.
In vitro addition of Ca2+ ions was effective in almost doubling binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) before equilibrium to an ion channel associated with an N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors. The addition of inhibitors for phospholipase (PLase) A2 markedly reduced binding in the absence of added Ca2+ ions, while Ca2+ ions restored the reduction to the level found in the absence of the inhibitors. Pretreatment with PLases A2 and C but not D was effective in potentiating [3H]MK-801 binding in a biphasic manner at a concentration range of 5 mU/ml-10 U/ml. Moreover, PLases A2 and C at low concentrations not only suppressed the abilities of 3 different agonists to potentiate [3H]MK-801 binding before equilibrium, but also reduced that of Ca2+ ions. These results suggest that Ca2+ ions may potentiate [3H]MK-801 binding to the NMDA channel highly permeable to Ca2+ ions through a mechanism common to that underlying potentiation by exogenous PLase A2 and/or C.
Han
D
D
Department of Pharmacology, Setsunan University, Osaka, Japan.
Ogita
K
K
Yoneda
Y
Y
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010740:Phospholipases / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013570:Synaptic Membranes / Q000187:drug effects
D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D010740:Phospholipases; D010741:Phospholipases A; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D002118:Calcium