Binding Properties of 3-[125I]Iodophencyclidine, a New Radioligand for N-Methyl-D-Aspartate-Gated Ionic Channels |
| |
Authors: | Robert Chicheportiche Janique Guiramand Jean Marc Kamenka Michel Ponchant† Jean Pierre Beaucourt† |
| |
Institution: | INSERM U 336, Ecole Nationale Supérieure de Chimie de Montpellier, France. |
| |
Abstract: | The binding properties of the 125I-labeled phencyclidine derivative N-1-(3-125I]iodophenyl)cyclohexyl]piperidine (3-125I]iodo-PCP), a new ligand of the N-methyl-D-aspartate (NMDA)-gated ionic channel, were investigated. Association and dissociation kinetic curves of 3-125I]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 3-125I]iodo-PCP also were well described using two binding sites: one of a high affinity (KDH = 15.8 +/- 2.3 nM) and the other of a low affinity (KDL = 250 +/- 40 nM). 3-Iodo-PCP inhibited the binding of 3-125I]iodo-PCP with inhibition curves that were well fitted by a two-site model. The binding constants (KiH, BmaxH; KiL, BmaxL) so obtained were close to those obtained in saturation experiments. Ligands of NMDA-gated ionic channels also inhibited the binding of 3-125I]iodo-PCP with two constants, KiH and KiL. 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 3-125I]iodo-PCP with a high affinity. Moreover, the regional distribution of the high-affinity binding of 3-125I]-iodo-PCP paralleled that of tritiated N-1-(2-thienyl)cyclohexyl]piperidine (3H]TCP). In contrast to that of 3H] TCP, the binding of 3-125I]iodo-PCP to well-washed rat brain membranes was fast and insensitive to glutamate and glycine.(ABSTRACT TRUNCATED AT 250 WORDS) |
| |
Keywords: | Iodine-125 3-[125I]Iodophencyclidine binding Phencyclidine receptors N-Methyl-D-aspartate-gated ionic channels |
|
|