Binding studies and photoaffinity labeling identify two classes of phencyclidine receptors in rat brain.
Binding and photoaffinity labeling experiments were employed in order to differentiate 1-(1-phenylcyclohexyl)piperidine (PCP) receptor sites in rat brain. Two classes of PCP receptors were characterized and localized: one class binds [3H]-N-[1-(2-thienyl)cyclohexyl]piperidine [( 3H]TCP) with high affinity (Kd = 10-15 nM) and the other binds the ligand with a relatively low affinity (Kd = 80-100 nM). The two classes of sites have different patterns of distribution. Forebrain regions are characterized by high-affinity sites (hippocampus greater than frontal cortex greater than thalamus greater than olfactory bulb greater than hypothalamus), but some parts (e.g., hippocampus, hypothalamus) contain low-affinity sites as well. In the cerebellum only low-affinity sites were detected. Binding sites for [3H]PCP and for its photolabile analogue [3H]azido-PCP showed a regional distribution similar to that of the [3H]TCP sites. The neuroleptic drug haloperidol did not block binding to either the high- or the low-affinity [3H]TCP sites, whereas Ca2+ inhibited binding to both. Photoaffinity labeling of the PCP receptors with [3H]AZ-PCP indicated that five specifically labeled polypeptides of these receptors (Mr 90,000, 62,000, 49,000, 40,000, and 33,000) are unevenly distributed in the rat brain. Two of the stereoselectively labeled polypeptides (Mr 90,000 and 33,000) appear to be associated with the high- and low-affinity [3H]TCP-binding sites; the density of the Mr 90,000 polypeptide in various brain regions correlates well with the localization of the high-affinity sites, whereas the density of the Mr 33,000 polypeptide correlates best with the distribution of the low-affinity sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Haring
R
R
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Kloog
Y
Y
Kalir
A
A
Sokolovsky
M
M
D000345:Affinity Labels / Q000378:metabolism*; D000818:Animals; D001386:Azides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000302:isolation & purification / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D013574:Synaptosomes / Q000378:metabolism; D014018:Tissue Distribution
C040647:3-azidophencyclidine; D000345:Affinity Labels; D001386:Azides; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D010622:Phencyclidine; D002118:Calcium