Effect of spermine and N1-dansyl-spermine on epileptiform activity in mouse cortical slices.
N(1)-dansyl-spermine is a novel polyamine analogue, which has been demonstrated to have an antagonist action at the stimulatory polyamine site on the N-methyl-D-aspartate (NMDA) receptor macrocomplex. Cortical wedges from genetically epilepsy-prone DBA/2 mice demonstrate spontaneous epileptiform activity when perfused with Mg(2+)-free artificial cerebrospinal fluid (aCSF). This epileptiform activity has been demonstrated to be primarily mediated through the NMDA receptor. N(1)-dansyl-spermine reduced the spontaneous epileptiform activity at a high dose (100 microM) but had no effect at a lower dose (50 microM). The polyamine, spermine (300 microM) caused an increase in the rate of the spontaneous epileptiform discharges. This effect of spermine was antagonised by administration of the low dose of N(1)-dansyl-spermine (50 microM). This further demonstrates the role of the NMDA receptor in the production of spontaneous epileptiform discharges in the cortical wedge preparation and clearly illustrates both the facilitatory action of spermine and the polyamine antagonist action of N(1)-dansyl-spermine at the stimulatory polyamine site on the NMDA receptor.
Kirby
Brian P
BP
Department of Pharmacology, School of Pharmacy, Trinity College, Dublin, Ireland. bkirby@rcsi.ie
Shaw
Graham G
GG
D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D003619:Dansyl Compounds / Q000494:pharmacology*; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
D003619:Dansyl Compounds; C105932:N(1)-dansylspermine; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine