MODULATION OF [H-3] MK-801 BINDING BY POLYAMINES IN HUMAN-DEVELOPMENTAND AGING

[H-3]MK-801 binding was used as an index of N-methyl-D-aspartate chann el opening in frontal cortex homogenates under the modulatory influenc e of the polyamines spermine and spermidine, at three stages of human development and aging. [H-3]MK-801 binding in premature infant cases ( 22-38 weeks gestation) fell significantly with increasing concentratio ns of spermidine and spermine. In child/adult cases (6-40years) at con centrations of spermidine and spermine up to 50 mu M, significant stim ulation of [H-3]MK-801 binding occurred. In the oldest cases (55-84yea rs) there was no significant stimulation or inhibition of [H-3]MK-801 binding. The polyamine antagonist arcaine (100 mu M) reduced basal bin ding, and binding in the presence of spermidine in premature infants. In child/adult cases, arcaine antagonised the spermidine stimulation o f [H-3]MK-801 binding, but was less effective at concentrations of spe rmidine above 50 mu M. There are thus qualitative differences in the r esponse to polyamines between premature infants and adults which may b e important in the design of antiischaemic drugs whose mode of action is via the polyamine site of the N-methyl-D-aspartate receptor.