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)

1. The contractile and electrical responses to acetylcholine (ACh) in isolated segments of guinea-pig and rabbit coronary arteries were compared to those of the putative adenosine 5'-triphosphate (ATP)-dependent K+ channel opener, BRL 38227. 2. Both ACh and BRL 38227 produced concentration-dependent relaxation of vessel segments contracted with the H1-receptor agonist, 2-(2-aminoethyl)pyridine. 3. An IC90 of either vasodilator also produced 17-20 mV of hyperpolarization of the guinea-pig coronary artery. 4. Glibenclamide (1-35 microM) depolarized the guinea-pig coronary artery by 8-12 mV and antagonized BRL 38227- but not ACh-induced relaxation and hyperpolarization. 5. In the guinea-pig coronary artery, the K+ channel blockers phencyclidine (PCP, 100 microM), tetraethylammonium (TEA, 10 mM) and scorpion venom (8.7 micrograms ml-1) all significantly reduced ACh-induced relaxation and hyperpolarization whereas only PCP was an effective antagonist of both relaxation and hyperpolarization with BRL 38227. 6. Similar effects of glibenclamide and scorpion venom on ACh- and BRL 38227-induced relaxation were observed in the rabbit coronary artery. 7. Apamin (3.5 microM) was without effect on either the ACh- or BRL 38227-induced relaxation in the guinea-pig coronary artery. 8. In conclusion, the actions of BRL 38227 in coronary artery are compatible with its proposed effects on ATP-dependent K+ channels. In contrast, the results with ACh suggest that some step between the initial binding of ACh to endothelial muscarinic receptors and the final relaxation of the smooth muscle depends upon the opening of Ca(2+)-activated K+ channels.
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PMID:Comparison of the actions of acetylcholine and BRL 38227 in the guinea-pig coronary artery. 150 34

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