POLYAMINE POTENTIATION AND INHIBITION OF NMDA-MEDIATED INCREASES OF INTRACELLULAR FREE CA2-NEURONS( IN CULTURED CHICK CORTICAL)

Polyamine potentiation and inhibition of N-methyl-D-aspartate (NMDA) r eceptor-mediated Ca?C changes was studied in cultured chick cortical n eurons. Spermidine and spermine potentiated the effect of saturating c oncentrations of NMDA and glycine. No effect of spermidine or spermine was observed in the absence of NMDA or in the presence of either kain ate or quisqualate. Similarly, antagonism of the NMDA receptor complex with dizocilpine (an open channel blocker), or with competitive antag onists to the NMDA or glycine binding sites greatly attenuated or comp letely abolished the combined effects of polyamines plus NMDA and glyc ine. N-Acetylspermine and N-acetylspermidine, in the presence or absen ce of NMDA and glycine, were without effect. These data strongly sugge st that spermidine and spermine are potent and selective agonists at t he polyamine binding site. Putrescine and diethylenetriamine were inef fective as antagonists of NMDA-mediated intracellular free Ca2+ increa ses in the presence or absence of added spermine or spermidine. Arcain e and 1,10-diaminodecane, however, antagonized NMDA-mediated intracell ular free Ca2+ increases in the presence and absence of spermine and s permidine, and therefore appear to act either as inverse agonists at t he polyamine binding site or as open channel blockers of the NMDA rece ptor.