Binding studies and photoaffinity labeling identify two classes of phencyclidine receptors in rat brain

Journal Article · Tue Sep 08 00:00:00 EDT 1987 · Biochemistry; (United States)

OSTI ID:5767342

Haring, R; Kloog, Y; Kalir, A; Sokolovsky, M

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 (/sup 3/H)-N-(1-(2-thienyl)cyclohexyl)piperidine ((/sup 3/H)TCP) with high affinity (K/sub d/ = 10-15 nM) and the other binds the ligand with a relatively low affinity (K/sub d/ = 80-100 nM). The two classes of sites have different patterns of distribution. Forebrain regions are characterized by high-affinity sites, but some parts contain low-affinity sites as well. In the cerebellum only low-affinity sites were detected. Binding sites for (/sup 3/H)PCP and for its photolabile analog (/sup 3/H)azido-PCP showed a regional distribution similar to that of the (/sup 3/H)TCP sites. The neuroleptic drug haloperidol did not block binding to either the high- or the low-affinity (/sup 3/H)TCP sites, whereas Ca/sup 2 +/ inhibited binding to both. Photoaffinity labeling of the PCP receptors with (/sup 3/H)AZ-PCP indicated that five specifically labeled polypeptides of these receptors are unevenly distributed in the rat brain. Two of the stereoselectively labeled polypeptides appear to be associated with the high- and low-affinity (/sup 3/H)TCP-binding sites; the density of the M/sub r/ 90,000 polypeptide in various brain regions correlates well with the localization of the high-affinity sites, whereas the density of the M/sub r/ 33,000 polypeptide correlates best with the distribution of the low-affinity sites. The results are compatible with the existence of two classes of PCP receptors in the rat brain, each having a distinct polypeptide that carries the ligand recognition site and has a selective localization in the brain.

• Research Organization: Tel Aviv Univ., Israel
• OSTI ID: 5767342
• Journal Information: Biochemistry; (United States), Vol. 26:18
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
RECEPTORS
MOLECULAR STRUCTURE
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS
AZIDO COMPOUNDS
BRAIN
LIGANDS
PIPERIDINES
RATS
AMINES
ANIMALS
AZINES
BODY
CENTRAL NERVOUS SYSTEM
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HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
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ORGANIC COMPOUNDS
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ORGANS
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