Human retina contains polyamine sensitive [3H]-ifenprodil binding sites: implications for neuroprotection?
OBJECTIVE
This study characterised the pharmacology of [3H]-ifenprodil binding to the polyamine binding sites (PBS) on the N-methyl-D-aspartate (NMDA) receptor channel complex on human retinas. These data were correlated with the known neuroprotective effects of ifenprodil and eliprodil.


METHODS
Specific binding of [3H]-ifenprodil (under sigma site blockade) was investigated using human retinal homogenates and radioligand binding techniques. Scatchard and competition analyses were utilised to define the pharmacology of the [3H]-ifenprodil binding sites.


RESULTS
Specific binding of [3H]-ifenprodil comprised 73% (SEM 3%) of total and reflected interaction with two affinity sites (Kds = 0.39 and 4.3 microM) of different densities (Bmax = 14.4 and 105 pmol/mg protein) (n = 5). The rank order of affinity of compounds competing for [3H]-ifenprodil binding to the high affinity PBS was: ifenprodil > eliprodil > arcaine > spermine > diaminodecane > spermidine > putrescine >> MK-801 (n = 3-7). However, [3H]-ifenprodil binding was minimally inhibited by glutamate, NMDA, and kainate.


CONCLUSIONS
These studies have shown, for the first time, the presence of specific [3H]-ifenprodil binding sites in the human retina with pharmacological characteristics of PBS associated with the NMDA receptor ionophore complex. The neuroprotective effects of eliprodil and ifenprodil may, in part, be mediated via these [3H]-ifenprodil labelled sites.
Sharif
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NA
Molecular Pharmacology Unit, Alcon Laboratories, Inc., Fort Worth, Texas 76134, USA.
Xu
S X
SX
D000368:Aged; D000369:Aged, 80 and over; D001645:Biguanides / Q000494:pharmacology; D001665:Binding Sites; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*
D001645:Biguanides; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010880:Piperidines; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; C006624:arcaine; D016202:N-Methylaspartate; C010739:ifenprodil; C058083:eliprodil