Identification and properties of phencyclidine-binding sites in nervous tissues.
[3H]Phencyclidine (PCP) binds to a single class of noninteracting binding sites in rat brain membranes with an affinity Kd of 0.25 microM and a maximal binding capacity BM of 2.4 pmol/mg of membrane protein. PCP derivatives also interact with the muscarinic and mu-opiate receptors in rat brain membranes with affinities that are one or two orders of magnitude lower than those observed for the [3H]PCP-binding sites. Activities of 25 PCP derivatives in the rotarod assay are closely correlated to affinities of these molecules for the [3H]PCP-binding sites, but not for the muscarinic or mu-opiate receptors. Monohydroxylation of PCP generally decreases the affinity of PCP for the [3H]PCP- and muscarinic-binding sites and does not change the affinity for the mu-opiate receptor. The metaphenolic derivative of PCP does not follow these general rules; the affinities of this derivative for the [3H]PCP- and mu-opiate-binding sites are 8 and 430 times higher, respectively, than those of PCP itself. Voltage-clamp experiments with N1E 115 neuroblastoma cells show that PCP is an efficient blocker of both the K+ channel (EC50 = 2.6 microM) and the Na+ channel (EC50 = 9.2 microM).
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000503:physiopathology; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship
D007473:Ion Channels; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D012964:Sodium; D010622:Phencyclidine; D011188:Potassium