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Polyamines potentiate NMDA induced whole-cell currents in cultured striatal neurons

https://doi.org/10.1016/0014-2999(90)90193-AGet rights and content

References (5)

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    Glycine potentiates the NMDA response in cultured mouse brain neurons

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  • R.W. Ransom et al.

    Cooperative modulation at [3H]-MK-801 binding to the NMDA receptor-ion channel complex by L-Glutamate, Glycine and polyamines

    J. Neurochem.

    (1988)
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    Spermine is best known as an endogenous pore blocker of cation-selective channels (12). However, spermine can also be released into the synapse in an activity-dependent fashion (12) where it may modify NMDA receptor synaptic transmission (13–17). Extracellular spermine is thought to bind to the ATDs of GluN1-GluN2B NMDA receptors (Fig. 1) and potentiates agonist-induced currents (13, 18).

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    Accordingly, polyamines, at low micromolar concentrations, enhance [3H]MK-801 and [3H]TCP binding to the NMDA receptor channel, whereas higher concentrations of polyamines do not alter the binding of these ligands, resulting in a biphasic concentration dose–response curve (Ransom & Stec, 1988; Sacaan & Johnson, 1990; Williams, 1997). Accordingly, low concentrations of polyamines enhance NMDA-evoked currents, whereas higher concentrations of polyamines produce less enhancement of, or inhibit, NMDA receptor currents (McGurk, Bennett, & Zukin, 1990; Rock & Macdonald, 1995; Sprosen & Woodruff, 1990; Williams, Dawson, Romano, Dichter, & Molinoff, 1990). Moreover, these results agree with previous studies that have shown that intrahippocampal or intra-amygdala administration of SPD improves the memory of the inhibitory avoidance task (Berlese et al., 2005; Rubin et al., 2000) and fear conditioning (Rubin et al., 2004) in a biphasic manner.

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    Polyamines enhance [3H]MK-801 and [3H]TCP binding to the NMDA receptor at low micromolar concentrations but, at high concentrations, do not alter the binding of these ligands (Ransom and Stec, 1988; Sacaan and Johnson, 1990b; Williams, 1997a,b). Accordingly, while low concentrations of polyamine spermidine enhance NMDA-evoked currents, high concentrations produce less enhancement or inhibit such currents (Rock and Macdonald, 1995; Sprosen and Woodruff, 1990; Williams, 1997b). Considering that spermidine positively modulates NMDA receptor conductance, we investigated whether the inhibitory effect of spermidine on the Na+,K+-ATPase activity involved NMDA receptor-mediated mechanisms.

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