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Binding Properties of 3‐[ 125 I]Iodophencyclidine, a New Radioligand for N ‐Methyl‐D‐Aspartate‐Gated Ionic Channels
Author(s) -
Chicheportiche Robert,
Guiramand Janique,
Kamenka Jean Marc,
Ponchant Michel,
Beaucourt Jean Pierre
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09397.x
Subject(s) - phencyclidine , chemistry , radioligand , nmda receptor , stereochemistry , dissociation constant , binding site , dissociation (chemistry) , ligand (biochemistry) , radioligand assay , receptor , biochemistry
The binding properties of the 125 l‐labeled phencyclidine derivative N ‐[1‐(3‐[ 125 I] iodophenyl)cyclohexyl] piperidine (3‐[ 125 I]iodo‐PCP), a new ligand of the N ‐methyl‐D‐aspartate (NMDA)‐gated ionic channel, were investigated. Association and dissociation kinetic curves of 3‐[ 125 I]iodo‐PCP with rat brain homogenates were well described by two components. About 32% of the binding was of fast association and fast dissociation, and the remaining binding was of slow association and slow dissociation. Saturation curves of 3‐[ 125 I] iodo‐PCP also were well described using two binding sites: one of a high affinity (K DH = 15.8 ± 2.3 n M ) and the other of a low affinity (K DL = 250 ± 40 n M ). 3‐Iodo‐PCP inhibited the binding of 3‐[ 125 I]iodo‐PCP with inhibition curves that were well fitted by a two‐site model. The binding constants (K iH , B maxH ; K iL , B maxL ) so obtained were close to those obtained in saturation experiments. Ligands of NMDA‐gated ionic channels also inhibited the binding of 3‐ [ 125 I]iodo‐PCP with two constants, K iH and K iL . There was a very good correlation (r = 0.987) between the affinities of these ligands to bind to NMDA‐gated ionic channels and their potencies to inhibit the binding of 3‐[ 125 I]iodo‐PCP with a high affinity. Moreover, the regional distribution of the high‐affinity binding of 3‐[ 125 I]‐iodo‐PCP paralleled that of tritiated N ‐[1‐(2‐thienyl)cyclohexyl]piperidine ([ 3 H]TCP). In contrast to that of [ 3 H]TCP, the binding of 3‐[ 125 I]iodo‐PCP to well‐washed rat brain membranes was fast and insensitive to glutamate and glycine. We conclude that 3‐[ 125 I]iodo‐PCP, at low concentrations, is suited for future rapid autoradio‐graphical studies of both open and closed forms of NMDA‐gated ionic channels and that 3‐[ 123 I]iodo‐PCP could be used successfully for in vivo studies by single‐photon emission computed tomography analysis.