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  • Title: Potentiation by polyamines of an interaction of noncompetitive antagonists at the N-methyl-D-aspartate receptor ionophore complex with phosphatidylserine.
    Author: Suzuki T, Ogita K, Yoneda Y.
    Journal: Neurochem Int; 1993 Nov; 23(5):427-40. PubMed ID: 7902748.
    Abstract:
    The addition of phosphatidylserine induced a significant interaction with radioligands widely used for labeling an ion channel associated with an N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors, such as [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) and [3H]N-[1-(2-thienyl)cyclohexyl]piperidine, in the absence of brain synaptic membranes irrespective of the addition of either L-glutamic acid or glycine when determined in the presence of the polyamine spermidine. The interaction with [3H]MK-801 increased in proportion to increasing concentrations of phosphatidylserine added at concentrations from 0.01 to 0.5 mg/ml. Similar interaction with [3H]MK-801 occurred for phosphatidylinositol to a lesser extent than for phosphatidylserine but not for either phosphatidylethanolamine or phosphatidylcholine at the similar concentration range. The interaction between phosphatidylserine and [3H]MK-801 was dependent partially on incubation temperature and on incubation time with reversible and saturable profiles. Among various natural and synthetic polyamines, both spermine and bis-(3-aminopropyl)amine in addition to spermidine were effective in markedly potentiating the interaction in a concentration-dependent manner at concentrations from 1 microM to 10 mM. However, the potentiation by spermidine was insensitive to antagonism by the respective antagonists for the NMDA and glycine domains at 0.1 mM. Moreover, the interaction between phosphatidylserine and [3H]MK-801 was sensitive to inhibition by several compounds with an antagonistic activity at calmodulin. The addition of phosphatidylserine completely concealed the potentiation by either glutamate alone or both glutamate and glycine of the binding of [3H]MK-801 in brain synaptic membranes with concomitant enhancement of the ability of spermidine to potentiate the binding, while phosphatidylserine failed to affect the affinities of the respective ligands for the NMDA and glycine domains. These results suggest that the acidic phospholipid phosphatidylserine may at least in part play crucial roles in mechanisms underlying the potentiation by polyamines of the binding of [3H]MK-801 to the open NMDA channel in rat brain.
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