PCP site 2: a high affinity MK-801-insensitive phencyclidine binding site

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Phencyclidine (PCP) is a psychotomimetic drug with anticonvulsant and neuroprotective effects.
• PCP interacts with various central nervous system (CNS) macromolecules, including NMDA receptors, ion channels, and biogenic amine transporters.

Purpose of the Study:

• To investigate the existence and characteristics of a PCP binding site associated with biogenic amine transporters.
• To differentiate this novel binding site from the NMDA receptor/ionophore complex.

Main Methods:

• Utilized ligand binding studies with a PCP analog, [3H]1-[1-(2-thienyl)cyclohexyl]piperidine.
• Analyzed the ligand selectivity of the identified binding site.
• Correlated binding affinities with inhibition of [3H]dopamine uptake.

Main Results:

• Identified a distinct PCP binding site, designated PCP site 2, separate from the NMDA receptor/ionophore complex.
• Demonstrated that PCP site 2 exhibits ligand selectivity consistent with association with biogenic amine transporters.
• Showed a strong correlation between arylcycloalkylamine affinity for PCP binding sites and inhibition of dopamine uptake.

Conclusions:

• Phencyclidine (PCP) binds to a novel site (PCP site 2) in the CNS.
• PCP site 2 is associated with biogenic amine transporters, not the NMDA receptor.
• This finding provides insights into the molecular targets of PCP and related compounds.