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)

The effects of three irreversible anticholinesterase agents, echothiophate (217MI), tertiary methylamine analog of 217MI (217AO) and Tetram, on end plate currents (e.p.c.s) of Rana pipiens cutaneous pectoris muscle were studied using electrophysiological techniques. All three compounds (217MI, 1-10 microM; 217AO, 1-25 microM; and Tetram, 1-50 microM) decreased the rate of e.p.c. decay (alpha) to the same extent as neostigmine (10 microM), a reversible anticholinesterase agent. Decay remained a single exponential at all membrane potentials. 217MI and its derivatives greatly reduced the normal voltage dependence of alpha represented by the slope (H = mV-1) of log alpha vs. membrane potential, in contrast to neostigmine which had no effect on H. Suppression of Ach release by the addition of 4 mM Mg++ to end-plates did not alter the reduction of H by 217AO indicating that the anticholinesterase-induced decrease in H is not simply due to an increased interaction between Ach and its receptors. Additionally, the pretreatment of end-plates with methanesulfonyl fluoride, also an irreversible cholinesterase agent, did not modify the effects of 217AO and Tetram on H. 217MI and its derivatives, at low concentrations which altered H, did not affect [3H]PCP or [125I]alpha-bungarotoxin binding to Torpedo californica Ach receptor-rich membranes. It is concluded that these agents alter H by an effect on the Ach receptor ion channel complex unrelated to either esterase inhibition or channel block.
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PMID:Echothiophate and cogeners decrease the voltage dependence of end-plate current decay in frog skeletal muscle. 248 Oct 33

An autoradiographic analysis of high-affinity binding sites for the vesicular acetylcholine transport blocker [3H]vesamicol (2-(4-phenylpiperidino) cyclohexanol; AH 5183) was conducted in rat brain. [3H]Vesamicol binding was displaced 52-99% by DPPN [( 2,3,4,8]-decahydro-3-(4-phenyl-1-piperidinyl)-2-napthalenol) (IC50 = 14 nM) and by ketanserin (500 nM), haloperidol (43 nM), and vesamicol analogs, but not by drugs selective for adenosine, adrenergic, amino acid, calcium channel, monoaminergic, opioid, PCP, sigma, or several other receptor classes. [3H]Vesamicol binding was most concentrated in the interpeduncular nucleus and fifth and seventh cranial nerve nuclei. Moderate binding was found in the lateral caudate-putamen, medial nucleus accumbens, olfactory tubercle, vertical and horizontal diagonal bands of Broca, and basolateral amygdala. The distribution of [3H]vesamicol binding was similar to distributions of acetylcholine (r = 0.88), acetylcholine esterase (r = 0.97), choline acetyltransferase (ChAT) (r = 0.97), and [3H]hemicholinium-3 binding sites (r = 0.95-0.99). Lower correlations were obtained between [3H]vesamicol and muscarinic receptor densities (r = 0.50-0.70). Few exceptions to the match between binding and cholinergic neuronal markers were found, e.g., the molecular layer of the cerebellum and the thalamus. Lesions of cholinergic neuronal projections to the neocortex or hippocampus reduced [3H]vesamicol binding in each of these regions, but to a lesser extent than reductions in ChAT. [3H]Vesamicol binding sites appear to be anatomically associated with brain cholinergic neurons, a locus that is consistent with the control by this site of vesicular acetylcholine uptake.
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PMID:[3H]vesamicol binding in brain: autoradiographic distribution, pharmacology, and effects of cholinergic lesions. 297 45

The effect of several cytochrome P450 (P450) inducers on cocaine metabolism were examined in order to characterize the metabolic events contributing to cocaine-induced hepatotoxicity. Phenobarbital (PB)-pretreatment of mice induced P450s 3A and 2B and markedly increased serum alanine aminotransferase (ALT) activity after cocaine or norcocaine administration. Although dexamethasone (Dex) induced P450s 3A and 2B at least to the same extent as PB, no increase in serum ALT activity was observed after cocaine or norcocaine administration. Phencyclidine (PCP) pretreatment did not increase either P450s 3A or 2B, yet it markedly enhanced cocaine- or norcocaine-induced serum ALT activity. In contrast to the marked induction of P450s 3A and 2B, P450 2C was increased only 2.5-fold by PB and to an even lesser extent by Dex or PCP. Cannabidiol (CBD), which inactivates P450s 3A and 2C in mice, completely protected mice against cocaine- or norcocaine-induced hepatotoxicity irrespective of whether they were induced or not with PB or PCP. Both PB and Dex pretreatment increased the in vitro hepatic microsomal formation of the first two sequential oxidative metabolites of cocaine (norcocaine and N-hydroxynorcocaine), whereas PCP pretreatment did not. Hepatic esterase activity was also determined after pretreatment with P450 inducers, since this is the major detoxification pathway in cocaine metabolism. Dex pretreatment markedly increased (> 11-fold) total hepatic esterase activity, whereas PB pretreatment increased it more modestly (less than fourfold) and PCP pretreatment had little effect. This marked effect of Dex pretreatment may decrease liver cocaine concentrations and thus protect mice against cocaine-induced hepatotoxicity, despite their increased P450 2B and 3A contents.
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PMID:Effect of cytochrome P450 inducers on cocaine-mediated hepatotoxicity. 963 Apr 65

The putative hydrolase gene bhp from the balhimycin biosynthetic gene cluster has been cloned and overexpressed in Escherichia coli. The corresponding enzyme Bhp was purified to homogeneity by nickel-chelating chromatography and characterized. Although Bhp has sequence similarities to hydrolases with "haloperoxidase"/perhydrolase activity, it did not show any enzymatic activity with standard "haloperoxidase"/perhydrolase substrates (e.g., monochlorodimedone and phenol red), nonspecific esterase substrates (such as p-nitrophenyl acetate, p-nitrophenyl phosphate and S-thiophenyl acetate) or the model lactonase substrate dihydrocoumarin. However, Bhp could be shown to catalyse the hydrolysis of S-beta-hydroxytyrosyl-N-acetyl cysteamine thioester (beta-OH-Tyr-SNAC) with 15 times the efficiency of S-L-tyrosyl-N-acetyl cysteamine thioester (L-Tyr-SNAC). This is in agreement with the suggestion that Bhp is involved in balhimycin biosynthesis, during which it was supposed to catalyse the hydrolysis of beta-OH-Tyr-S-PCP (PCP=peptidyl carrier protein) to free beta-hydroxytyrosine (beta-OH-Tyr) and strongly suggests that Bhp is a thioesterase with high substrate specificity for PCP-bound beta-OH-Tyr and not a "haloperoxidase"/perhydrolase or nonspecific esterase.
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PMID:The thioesterase Bhp is involved in the formation of beta-hydroxytyrosine during balhimycin biosynthesis in Amycolatopsis balhimycina. 1999

Bacterial plasmids and phages encode the synthesis of toxic molecules that inhibit protozoan predation. One such toxic molecule is violacein, a purple pigmented, anti-tumour antibiotic produced by the Gram-negative soil bacterium Chromobacterium violaceum. In the current experiments a range of Escherichia coli K12 strains were genetically engineered to produce violacein and a number of its coloured, biosynthetic intermediates. A bactivorous predatory protozoan isolate, Colpoda sp.A4, was isolated from soil and tested for its ability to 'graze' on various violacein producing strains of E. coli K12. A grazing assay was developed based on protozoan "plaque" formation. Using this assay, E. coli K12 strains producing violacein were highly resistant to protozoan predation. However E. coli K12 strains producing violacein intermediates, showed low or no resistance to predation. In separate experiments, when either erythromycin or pentachlorophenol were added to the plaque assay medium, protozoan predation of E. coli K12 was markedly reduced. The inhibitory effects of these two molecules were removed if E. coli K12 strains were genetically engineered to inactivate the toxic molecules. In the case of erythromycin, the E. coli K12 assay strain was engineered to produce an erythromycin inactivating esterase, PlpA. For pentachlorophenol, the E. coli K12 assay strain was engineered to produce a PCP inactivating enzyme pentachlorophenol-4-monooxygenase (PcpB). This study indicates that in environments containing large numbers of protozoa, bacteria which use efflux pumps to remove toxins unchanged from the cell may have an evolutionary advantage over bacteria which enzymatically inactivate toxins.
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PMID:Plasmid encoded antibiotics inhibit protozoan predation of Escherichia coli K12. 2183 10