Human retina contains polyamine sensitive [H-3]-ifenprodil binding sites: implications for neuroprotection?

Aims-This study characterised the pharmacology of [H-3]-ifenprodil binding to the polyamine binding sites (PBS) on the N-methyl-D-aspartate (NMDA) rec eptor channel complex on human retinas. These data were correlated with the known neuroprotective effects of ifenprodil and eliprodil. Methods-Specific binding of [H-3]ifenprodil (under sigma site blockade) was investigated using human retinal homogenates and radioligand binding techn iques. Scatchard and competition analyses were utilised to define the pharm acology of the [H-3]-ifenprodil binding sites. Results-Specific binding of [H-3]ifenprodil comprised 73% (SEM 3%) of total and reflected interaction with two affinity sites (K(d)s = 0.39 and 4.3 mu M) of different densities (B-max = 14.4 and 105 pmol/mg protein) (n = 5). The rank order of affinity of compounds competing for [H-3]ifenprodil bindi ng to the high affinity PBS was: ifenprodil > eliprodil > arcaine > spermin e > diaminodecane > spermidine > putrescine much greater than MK-801 (n = 3 -7). However, [H-3]-ifenprodil binding was minimally inhibited by glutamate , NMDA, and kainate. Conclusion-These studies have shown, for the first time, the presence of sp ecific [H-3]-ifenprodil binding sites in the human retina with pharmacologi cal characteristics of PBS associated with the NMDA receptor ionophore comp lex. The neuroprotective effects of eliprodil and ifenprodil may, in part, be mediated via these [H-3]-ifenprodil labelled sites.