Multiple mode of binding of phencyclidines: High affinity association between phencyclidine receptors in rat brain and a monovalent ion-sensitive polypeptide

Two populations of phencyclidine (PCP) binding sites are shown to exist in the rat brain: a high-affinity monovalent ion-sensitive site (K_d of 10-14 nM for [³H]TCP, [³H]N-[1-(2-thienyl)cyclohexyl]piperidine), which exists in both the frontal cortex and the hippocampus, and a lower affinity site (K_d of 80-130 nM for [³H]TCP) which is found in the hippocampus but not in the frontal cortex. The nature of the interactions between the ion-binding sites and the high affinity PCP receptors depend on both ligand structure (PCP or TCP) and the ion involved (K⁺ or Na⁺). The high-affinity sites are associated with an Mr 90,000 polypeptide whose labeling by [³H]azido phencyclidine is selectively inhibited by monovalent ions.