m-Azido-phencyclidine covalently labels the rat brain PCP receptor, a putative K channel

摘要: Phencyclidine (PCP) is a schizophrenomimetic drug of abuse. PCP binds with high affinity (apparent dissociation constant, KD less than 10(-6) M) to rat brain membranes and blocks, selectively, voltage-gated, noninactivating K channel found in synaptosomes (presynaptic nerve terminals). Thus, it has been proposed that the high-affinity receptor this channel. Consistent hypothesis, we now show several blockers displace 3H-PCP from receptor. Additionally, have used photolabile analog PCP, m-azido-PCP (Az-PCP), identify receptor/putative In dark, Az-PCP bound reversibly 2 classes sites on synaptic [KD = 0.14 +/- 0.01 microM (n 5) for binding, 255 55 low-affinity binding]. Competitive binding studies between Az-3H-PCP nonlabeled analogs, tritiated indicated site high- Several amino-pyridines (APs) tetraalkylamines (TAAs), which are known block channels excitable cells, were also its membranes. The rank order potency displacement APs was 4- AP approximately equal 3,4-diAP greater 2-AP much 3-AP; TAAs TBA TEA TMA (the tetra-butyl, ethyl, methyl amines, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)