Binding properties of 3-[125I]iodophencyclidine, a new radioligand for N-methyl-D-aspartate-gated ionic channels.
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)
Chicheportiche
R
R
INSERM U 336, Ecole Nationale Supérieure de Chimie de Montpellier, France.
Guiramand
J
J
Kamenka
J M
JM
Ponchant
M
M
Beaucourt
J P
JP
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D005971:Glutamates / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D007457:Iodine Radioisotopes; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains
D005971:Glutamates; D007457:Iodine Radioisotopes; D007473:Ion Channels; D016202:N-Methylaspartate; D005998:Glycine