The rat brain phencyclidine (PCP) receptor. A putative K+ channel.

Receptor binding studies were carried out to test whether the rat brain phencyclidine (PCP) receptor is part of a K+ channel. [3H]PCP, and two analogs, [3H]TCP and m-amino[3H]PCP, labeled a single receptor on rat brain synaptic membranes. Each compound bound to a similar number of sites (Bmax = 2.7 pmol bound/mg protein); the apparent dissociation constants for these compounds (KD less than 0.3 microM) decreased with increasing temperature. The following observations indicate that the PCP receptor is part of a K+ channel: (1) aminopyridines (AP) and tetraalkylammonium ions blocked [3H]PCP binding; their respective orders of potency, 4-AP = 3,4-diAP much greater than 3-AP, and tetrabutylammonium (TBA) greater than tetraethylammonium much greater than tetramethylammonium, paralleled their abilities to block K+ channels, (2) the order of potency of PCP and its analogs for binding to the PCP receptor, TCP greater than PCE greater than m-amino-PCP greater than PCP greater than PCPY greater than m-nitro-PCP, paralleled their rank order for blocking brain K+ channels, and (3) the stereospecific displacement of [3H]PCP binding by the isomers of the "sigma" ligands, (+)N-allyl-normetazocine (NANM) greater than (-)NANM, and (-)cyclazocine greater than (+)cyclazocine, and of the dioxolanes, dexoxadrol much greater than levoxadrol, paralleled their abilities to block brain K+ channels. Reciprocal plot and Schild plot analyses indicated that TBA, (+)NANM and dexoxadrol were competitive inhibitors at the PCP receptor, whereas 4-AP had an allosteric interaction.