Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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, a voltage-gated, noninactivating K channel found in rat brain synaptosomes (presynaptic nerve terminals). Thus, it has been proposed that the high-affinity PCP receptor in brain is this K channel. Consistent with this hypothesis, we now show that several K channel blockers displace 3H-PCP from the rat brain receptor. Additionally, we have used a photolabile analog of PCP, m-azido-PCP (Az-PCP), to identify the brain PCP receptor/putative K channel. In the dark, Az-PCP bound reversibly to 2 classes of sites on rat brain synaptic membranes [KD = 0.14 +/- 0.01 microM (n = 5) for high-affinity binding, and KD = 255 +/- 55 microM for low-affinity binding]. Competitive binding studies between Az-3H-PCP and nonlabeled PCP analogs, and between Az-PCP and several tritiated PCP analogs, indicated that the high-affinity Az-PCP binding site is the high-affinity PCP receptor. Several amino-pyridines (APs) and tetraalkylamines (TAAs), which are known to block K channels in excitable cells, were also found to displace 3H-PCP from its high-affinity binding site on rat brain synaptic membranes. The rank order of potency for displacement of 3H-PCP from this site for the APs was 4-AP approximately equal to 3,4-diAP greater than 2-AP much greater than 3-AP; for the TAAs it was TBA greater than TEA much greater than TMA (the tetra-butyl, ethyl, and methyl amines, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:m-Azido-phencyclidine covalently labels the rat brain PCP receptor, a putative K channel. 243 4

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.
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PMID:The rat brain phencyclidine (PCP) receptor. A putative K+ channel. 244 95

The effects of phencyclidine(PCP) on the post-tetanic potentiation(PTP) of twitch tension were studied on the isolated mouse phrenic nerve diaphragm preparation. Phencyclidine increased directly elicited twitch tension while it decreased post-tetanic potentiation of the indirectly elicited twitch tension. The maximal depression effect of the PTP was found after higher frequencies and longer durations of stimulation. After repetitive stimulation, the amplitude of endplate potential was potentiated. Phencyclidine decreased the post-tetanic potentiation of the amplitude of endplate potential while the quantal content of the endplate potential was not affected. 4-Aminopyridine increased both directly and indirectly elicited twitch tension while it did not inhibit the post-tetanic potentiation of the twitch tension. It is concluded that phencyclidine suppressed the post-tetanic potentiation of the indirectly elicited twitch tension. The depressant effect may be mainly due to its effect on the acetylcholine receptor-ionic channel complex of the motor endplate.
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PMID:Effect of phencyclidine on post-tetanic twitch tension of the mouse diaphragm preparation. 303 6

Activation of the sympathetic system by phencyclidine (PCP) should result in catecholamine release from the adrenals. However, adrenalectomy does not reduce PCP-induced hypertension. In an attempt to rectify this inconsistency, the direct effects of PCP on the bovine adrenal medulla were examined. At (3 X 10(-6) M), PCP reduced the acetylcholine-(ACh)-induced catecholamine release by 50%. Surprisingly, barium-induced secretion of catecholamines was also reduced by PCP. ACh-induced catecholamine release was not altered by 10(-3)M 4-aminopyridine (4 AP), the potassium channel blocker. Thus, calcium antagonist actions of PCP and consequent block of catecholamine secretion from adrenal medulla may explain the lack of effect of adrenalectomy on PCP-induced hypertension. Possible contributions of calcium and/or potassium channel blockade to other manifestations of PCP overdosage are discussed.
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PMID:Block by phencyclidine of acetylcholine and barium induced adrenal catecholamine secretion. 688 80