Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Azocines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed2006

Enantioseparation of tetrahydropalmatine and Tröger's base by molecularly imprinted monolith in capillary electrochromatography.

Two chiral compounds, Tröger's base and tetrahydropalmatine, were enantioseparated on the (5S, 11S)-(-)-Tröger's base and l-tetrahydropalmatine imprinted monolithic capillary columns with CEC, respectively. The monoliths were prepared by in situ thermal-initiated copolymerization of methacrylic acid (MAA) and ethylene dimethacrylate (EDMA). After optimizing the ratio of porogens (toluene and dodecanol), the obtained monolithic capillary columns show good flow-through property and enantioselectivity. The influences of CEC parameters such as pH of the buffer, organic solvent and salt concentration on the electroosmotic flow (EOF) and recognition selectivity were systematically investigated. Under the optimal conditions, baseline resolutions of two chiral compounds were achieved. In addition, the fast separation was obtained within 4 min by applying higher voltage and assisting pressure of 6 bar.

Acetonitriles↗
PubMed2006

Comparison of biotic and abiotic treatment approaches for co-mingled perchlorate, nitrate, and nitramine explosives in groundwater.

Biological and abiotic approaches for treating co-mingled perchlorate, nitrate, and nitramine explosives in groundwater were compared in microcosm and column studies. In microcosms, microscale zero-valent iron (mZVI), nanoscale zero-valent iron (nZVI), and nickel catalyzed the reduction of RDX and HMX from initial concentrations of 9 and 1 mg/L, respectively, to below detection (0.02 mg/L), within 2 h. The mZVI and nZVI also degraded nitrate (3 mg/L) to below 0.4 mg/L, but none of the metal catalysts were observed to appreciably reduce perchlorate ( approximately 5 mg/L) in microcosms. Perchlorate losses were observed after approximately 2 months in columns of aquifer solids treated with mZVI, but this decline appears to be the result of biodegradation rather than abiotic reduction. An emulsified vegetable oil substrate was observed to effectively promote the biological reduction of nitrate, RDX and perchlorate in microcosms, and all four target contaminants in the flow-through columns. Nitrate and perchlorate were biodegraded most rapidly, followed by RDX and then HMX, although the rates of biological reduction for the nitramine explosives were appreciably slower than observed for mZVI or nickel. A model was developed to compare contaminant degradation mechanisms and rates between the biotic and abiotic treatments.

Aniline Compounds↗
PubMed2006

Remediation of RDX- and HMX-contaminated groundwater using organic mulch permeable reactive barriers.

Organic mulch is a complex organic material that is typically populated with its own consortium of microorganisms. The organisms in mulch breakdown complex organics to soluble carbon, which can then be used by these and other microorganisms as an electron donor for treating RDX and HMX via reductive pathways. A bench-scale treatability study with organic mulch was conducted for the treatment of RDX- and HMX-contaminated groundwater obtained from a plume at the Pueblo Chemical Depot (PCD) in Pueblo, Colorado. The site-specific cleanup criteria of 0.55 ppb RDX and 602 ppb HMX were used as the logical goals of the study. Column flow-through tests were run to steady-state at the average site seepage velocity, using a 70%:30% (vol.:vol.) mulch:pea gravel packing to approach the formation's permeability. Significant results included: (1) Complete removal of 90 ppb influent RDX and 8 ppb influent HMX in steady-state mulch column effluent; (2) pseudo-first-order steady-state kinetic rate constant, k, of 0.20 to 0.27 h(-1) based on RDX data, using triplicate parallel column runs; (3) accumulation of reduced RDX intermediates in the steady-state column effluent at less than 2% of the influent RDX mass; (4) no binding of RDX to the column fill material; and (5) no leaching of RDX, HMX or reduction intermediates from the column fill material. The results of the bench-scale study will be used to design and implement a pilot-scale organic mulch/pea gravel permeable reactive barrier (PRB) at the site.

Azocines↗
PubMed2004

Thermal reactive hazards of HMX with contaminants.

In the past, many unexpected runaway accidents occurred in manufacturing processes, involving volatile chemical and explosive storage and transportation. Incompatible product reactions of high explosives must be carefully considered using loss prevention strategies for thermal hazards risk analysis. High explosive reactions vary via environmental changes, contact materials, or process situations, such as onset temperature and shifts in reaction type when high explosives are in contact with contaminants. Therefore, the manufacture and handling of high explosives require the utmost in safety and loss prevention. HMX (cyclotetramethyene tetranitramine) is one kind of high explosive widely used around the world which is stable with high detonation strength properties. In this study, the influences of contaminants on HMX are investigated. The studied contaminants include ferrous chloride tetrahydrate, ferric chloride hexahydrate, acetone solution, acetic acid, and nitric acid. DSC thermal curves and incompatible reaction kinetic evaluations were preformed using iron, chlorine and acid. Organic acetone solution has lesser effects on HMX. Hopefully, this study will lead to improved thermal hazards risk analysis and reduce accidents.

Accidents, Occupational↗
PubMed2005

Evidence for functional nicotinic receptors on pancreatic beta cells.

Epidemiological studies associate smoking with reduced insulin secretion. We hypothesized that nicotine could negatively affect pancreatic beta-cell function. Acute or 48-hour exposures to nicotine (10(-4) to 10(-6) mol/L) moderately inhibited insulin release at basal (3.3 mmol/L) and/or elevated (27 mmol/L) glucose in rat and human islets. Acute exposure to nicotine (10(-6) mol/L) inhibited tolbutamide (200 micromol/L)-induced insulin release by 41% (P < .05), but did not affect secretion induced by KCl (20 mmol/L) or 3-isobutyl-1-methylxanthine (1 mmol/L) (tested in rat islets). Specific binding of [3H]nicotine was demonstrated in rat islets and in a beta -cell line of rat origin, INS-1. Such binding was enhanced by 48 hours of coculture with nicotine (10(-7) mol/L). Expression of mRNA for the nicotinic receptor subunits alpha 2, alpha 3, alpha 4, alpha 5, alpha 7, and beta 2 was detected in INS-1 cells by reverse transcriptase polymerase chain reaction. Acute exposure to cytisine (10(-6) mol/L), an agonist of alpha 4, beta 2 subunits, partially inhibited tolbutamide-induced insulin release. Specific binding of alpha bungarotoxin (10(-10) mol/L), an antagonist of the alpha 7 subunit, could be demonstrated in INS-1 cells, and culture with alpha bungarotoxin modestly increased insulin release in postculture incubations at basal and elevated glucose, P < .05. Our data indicate that functional nicotinic receptors are present in pancreatic islets and beta cells.

Adenosine Triphosphate↗
PubMed2006

Cyclophane and acyclic cyclophane: novel channel blockers of N-methyl-D-aspartate receptor.

The effects of cyclophanes (CPCn, CPPy and TGDMAP) and acyclic cyclophane (ATGDMAP) on various glutamate receptors were studied with these receptors expressed in Xenopus oocytes using voltage-clamp recording. CPCn, CPPy, TGDMAP and ATGDMAP were found to inhibit macroscopic currents at heteromeric NMDA receptors (NR1/NR2), but not Ca(2+)-permeable AMPA receptors (GluR1), Ca(2+)-nonpermeable AMPA receptors (GluR1/GluR2) and metabotropic glutamate receptors (mGluR1alpha). The inhibition of NR1/NR2A receptors by these compounds was more potent than those of the other NMDA receptor subtypes. At a resting potential (-70 mV), the IC(50) values of CPCn, CPPy, TGDMAP and ATGDMAP for NR1/NR2A receptors were 0.5+/-0.1, 1.0+/-0.2, 8.0+/-0.8 and 4.9+/-0.5 microM, respectively. The inhibition by these compounds was voltage-dependent, that is, the degree of inhibition was in the order of negative holding potentials, -100 mV>-70 mV>-20 mV. Results of experiments using mutant NR1 and NR2 subunits identified residues that influence block by CPCn. The inhibition by CPCn was not altered significantly in the mutants at the critical asparagines in the M2 loop, NR1 N616, NR2B N615 and NR2B N616, these residues are known to form the narrowest region of the channel and the binding site of Mg(2+). However, mutations at NR1 N650, located in the vestibule of channel pore, and NR1 D669, located in the extracellular region, reduced the inhibition by CPCn, suggesting that these amino acid residues interact with CPCn. These results suggest that CPCn interacts directly with the mouth or vestibule of the ion channel, like a lid.

Animals↗
PubMed2004

Opposite conditioned place preference responses to endomorphin-1 and endomorphin-2 in the mouse.

An unbiased conditioned place preference paradigm was used to evaluate the reward effect of selective endogenous mu-opioid ligands, endomorphin-1 and endomorphin-2, in male CD-1 mice. Pre- and post-conditioning free-movement were measured on day 1 and day 5, respectively. Conditioning sessions were conducted twice daily from day 2 through day 4 consisting of the alternate injection of conditioning drug or vehicle. Intracerebroventricular (i.c.v.) injection of endomorphin-1 (0.3-10 microg) induced place preference in a dose-dependent manner; whereas, endomorphin-2 (1-10 microg) dose-dependently induced place aversion. Both endomorphin-1-induced place preference and endomorphin-2-induced place aversion were blocked by pretreatment i.c.v. with mu-opioid receptor antagonist, beta-funaltrexamine. Selective delta-opioid receptor antagonist, naltrindole, co-administered i.c.v. with endomorphin-1 or endomorphin-2 did not affect reward effect. However, endomorphin-2-induced place aversion, but not endomorphin-1-induced place preference, was blocked by the i.c.v.-administered selective kappa-opioid receptor antagonist, WIN 44,441-3. It is concluded that endomorphin-1 produces conditioned place preference, which is mediated by the stimulation of mu-, but not delta- or kappa-opioid receptors, while endomorphin-2 produces conditioned place aversion, which is mediated by the stimulation of mu- and kappa-, but not delta-opioid receptors.

Animals↗
PubMed2005

In vitro evidence and age-related changes for nicotinic but not muscarinic acetylcholine receptors in the central nervous system of Sepia officinalis.

Binding putative muscarinic ([3H]-NMS and [3H]-QNB) or nicotinic ([3H]-cytisine) acetylcholine receptors was quantitatively studied through the use of in vitro binding experiments on either membrane preparations or brain sections of juvenile (3 months), mature (15 months) or senescent (23 months) cuttlefish. No specific binding could be detected with muscarinic receptor ligands under any of the experimental conditions employed (ligand concentrations, buffers, ionic charges, types of tissue, i.e., brain sections or membrane preparations). On the other hand, [3H]-cytisine demonstrated a specific and saturable binding with a single class of high affinity binding sites (Kd of 2.6-34.6 nM; Bmax of 128-1682 fmol/mg tissue equivalent, depending on the central structure). This binding was found to be heterogeneous throughout the central regions (optic lobe>pedal lobe; superior frontal lobe>...precommissural lobe; vertical lobe>...anterior basal lobe; subvertical lobe; inferior frontal lobe; median basal lobe). These results question the existence of muscarinic-like receptors in the cuttlefish brain, or at least of a pharmacological dissimilarity from vertebrate muscarinic receptors. In contrast, nicotinic-like receptors are widely present; interestingly, their density was found to be significantly reduced in most nervous central lobes of senescent cuttlefish when compared with mature animals. The most significant decrease (-71%) was found in the anterior part of the superior frontal lobe, which is involved in visual learning; this might be related to the changes, previously demonstrated, in cholinergic neurons in this lobe in the course of aging.

Acetylcholine↗
PubMed2005

Subtypes of neuronal nicotinic acetylcholine receptors involved in nicotine-induced phosphorylation of extracellular signal-regulated protein kinase in PC12h cells.

Although many kinds of nicotinic acetylcholine receptor (nAChR) subtypes have been reported in the neuronal tissues, subtype differences in the nAChR-mediated intracellular signaling remains obscure. Using nAChR agonists and antagonists, the involvement of nAChRs in extracellular signal-regulated protein kinase (ERK) phosphorylation in PC12h cells was investigated. Cytisine and nicotine induced the phosphorylation of ERKs in a dose-dependent manner, whereas RJR-2403 had no effect. Cytisine, but not RJR-2403, also induced phosphorylation of CREB. Mecamylamine, dextromethorphan and 18-methoxycoronaridine inhibited nicotine-induced ERK phosphorylation with much higher affinity than dihydro-beta-erythroidine and alpha-conotoxin MII. These results suggest the involvement of alpha3beta4 nAChRs in ERK phosphorylation in PC12h cells.

Alkaloids↗
PubMed2006

Antisense knockdown of the rat alpha7 nicotinic acetylcholine receptor produces spatial memory impairment.

Selective and brain penetrating pharmacological antagonists for use in clarifying a role of alpha7 nicotinic acetylcholine receptors (nAChR) in behavioral paradigms are presently unavailable. Studies in alpha7 knock-out mice (KO) have not revealed convincing changes in behavioral phenotype, in particular measures of cognition that include contextual fear conditioning and spatial memory, which may be due to compensatory developmental changes. Therefore, an antisense oligonucleotide (aON) targeted toward the 3'- and 5'-UTR coding regions of the rat alpha7 nicotinic acetylcholine receptor was used. Following central injection of aON into the lateral ventricle of Long Evans rats for 6 days, treated rats exhibited a significant 42% and 25% decrease in alpha7 nAChR densities in hippocampus and cortex, respectively, as measured by [(3)H]-methyllycaconitine (MLA) binding. There was no change in alpha4beta2 densities measured by [(3)H]-cytisine binding. Acquisition of Morris Water Maze (MWM) performance, a measure of spatial memory, was impaired in aON-treated rats. In addition, a reduction in target platform crossings during a subsequent probe-trial was observed. These data demonstrate the ability of this aON to reduce hippocampal and cortical alpha7 nicotinic receptor densities associated with impaired MWM performance and support the specific involvement of the alpha7 nAChR in spatial learning and memory, a phenotype not affected in alpha7 KO mice.

Aconitine↗
PubMed2005

The subunit composition and pharmacology of alpha-Conotoxin MII-binding nicotinic acetylcholine receptors studied by a novel membrane-binding assay.

The subunit composition and pharmacology of alpha-Conotoxin MII-binding (alpha-CtxMII) nicotinic acetylcholine receptors (nAChR) was studied by an improved [(125)I]-alpha-CtxMII membrane binding method. This binding method facilitates pharmacological studies that have been difficult to accomplish with [(125)I]-alpha-CtxMII autoradiography or alpha-CtxMII inhibition of [(125)I]-epibatidine binding. Binding densities and K(d)-values obtained by this [(125)I]-alpha-CtxMII membrane binding were similar to the values obtained by autoradiography or alpha-CtxMII inhibition of [(125)I]-epibatidine binding, verifying that each of these approaches measures the same nAChR population. Binding results with nAChR subunit-null mutant mice confirm and extend observations from earlier studies: [(125)I]-alpha-CtxMII binding measures two sets of alpha6beta2* nAChR (alpha4alpha6beta2beta3 or alpha6beta2beta3). Most nicotinic agonists and antagonists show monophasic inhibition of [(125)I]-alpha-CtxMII binding, indicating that alpha4alpha6beta2beta3 and alpha6beta2beta3 have similar binding properties. Comparison of the binding and activation profiles of alpha6beta2* nAChR to those of other nAChR subtypes (alpha4beta2* and beta4*) indicates that these receptors have distinctly different pharmacology indicating that it may be possible to target alpha6beta2* nAChR selectively to develop compounds that might be therapeutically useful.

Acetylcholine↗
PubMed2006

Prenatal nicotine exposure alters the nicotinic receptor subtypes that modulate excitation of parasympathetic cardiac neurons in the nucleus ambiguus from primarily alpha3beta2 and/or alpha6betaX to alpha3beta4.

Nicotinic receptors play an essential role in central cardiorespiratory function, however, the types of nicotinic receptors responsible for activating cardiac vagal neurons in the nucleus ambiguus that control heart rate are unknown. This study tests whether alpha-conotoxin MII and alpha-conotoxin AuIB sensitive nicotinic receptors are involved in augmentation of glutamatergic neurotransmission and changes in holding current in cardiac vagal neurons, and whether exposure to nicotine in the prenatal period alters these responses. The nicotinic agonist cytisine significantly increased the holding current and amplitude of glutamatergic mEPSCs. In unexposed animals alpha-conotoxin MII (100nM) significantly reduced the increase in mEPSC amplitude and change in holding current evoked by cytisine. However, in animals prenatally exposed to nicotine, alpha-conotoxin MII blunted but did not block the increase in mEPSC amplitude but blocked the increase in holding current evoked by cytisine. In unexposed animals, alpha-conotoxin AuIB (10microM) blocked the cytisine evoked increase in mEPSC amplitude and inhibited but did not abolish the increase in holding current. In contrast, in animals exposed to nicotine, alpha-conotoxin AuIB blunted the increase in mEPSC amplitude, and completely abolished the cytisine evoked increase in holding current. These data demonstrate that the prenatal nicotine exposure alters the nicotinic receptors involved in excitation of cardiac vagal neurons.

Alkaloids↗
PubMed2005

Smoking during early pregnancy affects the expression pattern of both nicotinic and muscarinic acetylcholine receptors in human first trimester brainstem and cerebellum.

Prenatal nicotine exposure is associated with an increased risk of complications during pregnancy and childhood. In this study the expression of nicotinic and muscarinic acetylcholine receptors in first trimester pons, medulla oblongata and cerebellum from abortus (5-12 weeks of gestation) of smoking and nonsmoking women was compared. A significant age-related increase in binding of nicotinic receptor subtype alpha4 was found in both pons and cerebellum only in fetal tissue from non-smoking women, while a similar increase was observed in medulla oblongata from fetuses exposed to smoking. A significant age-related increase in binding of muscarinic receptor subtype m2 was observed in pons from abortus of smoking compared with non-smoking women. The gene expression pattern of both alpha4 and alpha7 nicotinic receptor subunits was changed after smoking in all three regions investigated. Smoking also changed the expression of m1 and 2 muscarinic receptor mRNA in pons, m1 mRNA in cerebellum and the m3 mRNA in medulla oblongata. The findings indicate that early prenatal nicotine exposure affects the normal developmental pattern of the cholinergic system in human fetal brain.

Alkaloids↗
PubMed2006

Age-related alterations of GABAergic input to CA1 pyramidal neurons and its control by nicotinic acetylcholine receptors in rat hippocampus.

The aim of this study was to determine whether age-associated alterations in the GABAergic input to pyramidal neurons in the hippocampus are due to a dysfunction of GABAergic interneurons, and/or a decrease in their cholinergic control via nicotinic receptors (nAChRs). Electrophysiological recordings were obtained from pyramidal cells in the CA1 area of hippocampal slices from young (3-4 months old) and aged (25-30 months old) Sprague-Dawley rats. Synaptic GABA(A) receptor-mediated inhibitory postsynaptic currents and inhibitory postsynaptic potentials induced by stimulation of the stratum oriens were significantly smaller in aged rats. The frequency (but not amplitude) of spontaneous and miniature GABA inhibitory postsynaptic currents (IPSCs) was reduced in aged rats, suggesting a presynaptic alteration. Tetanic stimulation of cholinergic afferents to release endogenous acetylcholine, or an exogenous application of the nAChR agonist cytisine, increased the frequency of spontaneous IPSCs in young rats; however these effects were not evident in aged rats, indicating that the nicotinic control of GABA release is lowered during aging. None of these age-related alterations were reversed by a chronic treatment with donepezil, a cholinesterase inhibitor. Immunofluorescent labeling of GABA interneurons with somatostatin (SOM), parvalbumin (PV) or calbindin (CB), together with the vesicular acetylcholine transporter VAChT, revealed a selective loss of subpopulations of SOM and CB positive interneurons. This loss was associated with a general decrease in density of the cholinergic network in aged rats. Thus, the lower GABAergic inhibition observed in the aged rat hippocampus is due to a selective loss/dysfunction of subpopulations of GABAergic interneurons, associated with a widespread cholinergic deficit.

Age Factors↗
PubMed2005

Portable remote Raman system for monitoring hydrocarbon, gas hydrates and explosives in the environment.

We report our initial efforts to use a small portable Raman system for stand-off detection and identification of various types of organic chemicals including benzene, toluene, ethyl benzene and xylenes (BTEX). Both fiber-optic (FO) coupled and a directly coupled f/2.2 spectrograph with the telescope have been developed and tested. A frequency-doubled Nd:YAG pulsed laser (20 Hz, 532 nm, 35 mJ/pulse) is used as the excitation source. The operational range of the FO coupled Raman system was tested to 66 m, and the directly coupled system was tested to a distance of 120 m. We have also measured remote Raman spectra of compressed methane gas and methane gas hydrate. The usefulness of the remote Raman system for identifying unknown compounds is demonstrated by measuring stand-off spectra of two plastic explosives, e.g. tri-amino tri-nitrobenzene (TATB) and beta-HMX at 10 m stand-off distance. The remote Raman system will be useful for terrestrial applications such as monitoring environmental pollution, in identifying unknown materials in public places in 10s or less, and for detecting hydrocarbon plumes and gas hydrates on planetary surfaces such as Mars.

Azocines↗
PubMed1998

Evidence for presynaptic cholinergic receptors in sympathetic nerves in human dental pulp.

The purpose of this study was to determine whether presynaptic cholinergic receptors are present in sympathetic nerves in human dental pulp. Pulp was incubated with [3H]noradrenaline (0.6 mumol/l) for 30 min and then superfused with Krebs' solution at 1.0 ml/min. Electrical stimulation (100 sec, 5 Hz) increased the overflow of [3H]noradrenaline into the superfusate. Carbachol (10 and 100 mumol/l), an agonist of muscarinic receptors, decreased the stimulation-induced (SI) overflow of 3H, an effect blocked by atropine but not hexamethonium. Carbachol, atropine and hexamethonium had no effect on the resting overflow. Nicotine (10 mumol/l) increased the resting overflow and inhibited the SI overflow, although the inhibition was variable. Cytisine, another agonist of nicotinic receptors, also increased the resting overflow, but did not affect the SI overflow. To ascertain whether the actions of nicotine and electrical stimulation were influenced by the release of nitric oxide (NO), the effects of an NO donor and two NO-synthase inhibitors were examined. With the exception of one of the NO-synthase inhibitors (L-NAME), the agents were without effect on the overflow of 3H in the absence or presence of nicotine. It was concluded that sympathetic nerves in human dental pulp possess (a) presynaptic muscarinic receptors that inhibit the SI release of noradrenaline, and (b) nicotinic receptors that evoke the release of noradrenaline and that inhibit the SI release of the transmitter. The results do not point to a significant role for NO in the effects of stimulation or nicotine on the overflow of 3H.

Adolescent↗
PubMed2003

Mechanism of xanthine oxidase catalyzed biotransformation of HMX under anaerobic conditions.

Enzyme catalyzed biotransformation of the energetic chemical octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is not known. The present study describes a xanthine oxidase (XO) catalyzed biotransformation of HMX to provide insight into the biodegradation pathway of this energetic chemical. The rates of biotransformation under aerobic and anaerobic conditions were 1.6+/-0.2 and 10.5+/-0.9 nmolh(-1)mgprotein(-1), respectively, indicating that anaerobic conditions favored the reaction. The biotransformation rate was about 6-fold higher using NADH as an electron-donor compared to xanthine. During the course of reaction, the products obtained were nitrite (NO(2)(-)), methylenedinitramine (MDNA), 4-nitro-2,4-diazabutanal (NDAB), formaldehyde (HCHO), nitrous oxide (N(2)O), formic acid (HCOOH), and ammonium (NH(4)(+)). The product distribution gave carbon and nitrogen mass-balances of 91% and 88%, respectively. A comparative study with native-, deflavo-, and desulfo-XO and the site-specific inhibition studies showed that HMX biotransformation occurred at the FAD-site of XO. Nitrite stoichiometry revealed that an initial single N-denitration step was sufficient for the spontaneous decomposition of HMX.

Azocines↗
PubMed2001

In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation.

In this study, we investigated the effects of nicotine on rat brain mitochondria. The polarographic studies determined the effects on the respiratory chain, whereas enzymatic assays and [3H]-nicotine binding allowed us to precisely identify its target and site of action. The measurements of oxygen consumption showed a significantly concentration-dependent inhibition by nicotine (EC50 was 4.95x10(-11) M), and a maximal decrease of 23.90% at 10(-7) M. Nicotine bound to complex I of the respiratory chain and inhibited the NADH-Ubiquinone reductase activity. We also showed that nicotine and NADH were competitive on complex I. Effects of cotinine, the main nicotine metabolite, and nornicotine, were also investigated: nornicotine inhibited the mitochondrial respiration whereas cotinine did not. Because the complex I generates superoxide anion, we investigated the effects of nicotine, following NBT oxidation, and showed that nicotine was able to inhibit this reactive oxygen species (ROS) generation by 15.74% with an EC50 of 2.02x10(-11) M. In conclusion, the present study shows that nicotine interacts with the complex I of brain mitochondrial respiratory chain and decreases ROS generation. This may explain a part of the beneficial and protective effects of nicotine in few neurodegenerative diseases, as suggested by many epidemiological studies.

Adenosine Triphosphatases↗