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The rat brain phencyclidine (PCP) receptor. A putative K+ channel
1Department of Physiology, University of Maryland, School of Medicine, Baltimore 21201.
Biochemical Pharmacology
|February 1, 1988
Summary
The phencyclidine (PCP) receptor in rat brains appears to be part of a potassium (K+) channel. Binding affinities of PCP analogs and other channel blockers support this K+ channel hypothesis.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- The phencyclidine (PCP) receptor is a binding site in the rat brain.
- Its precise function and relationship to ion channels remain under investigation.
Purpose of the Study:
- To investigate whether the rat brain phencyclidine (PCP) receptor is functionally associated with a potassium (K+) channel.
- To characterize the binding properties of PCP and its analogs at this receptor.
Main Methods:
- Conducted receptor binding studies using radiolabeled PCP and its analogs ([3H]PCP, [3H]TCP, m-amino[3H]PCP) on rat brain synaptic membranes.
- Assessed the effects of known K+ channel blockers (aminopyridines, tetraalkylammonium ions) and sigma ligands on [3H]PCP binding.
- Utilized reciprocal plot and Schild plot analyses to determine the nature of inhibitor interactions.
Main Results:
- PCP, TCP, and m-amino-PCP bound to a single receptor site with similar Bmax values.
- Aminopyridines and tetraalkylammonium ions inhibited [3H]PCP binding, with potencies mirroring their K+ channel blocking activities.
- The relative potencies of PCP analogs and stereoisomers of sigma ligands for receptor binding correlated with their K+ channel blocking effects.
Conclusions:
- The findings strongly suggest that the phencyclidine (PCP) receptor is an integral component of a K+ channel in the rat brain.
- Tetraalkylammonium ions, sigma ligands, and PCP analogs act as competitive inhibitors, while aminopyridines exhibit allosteric interactions.