Abstract:
:Nitric oxide (NO) plays an important role in the cytotoxic activity of macrophages towards tumour cells and microbial pathogens. We investigated whether alteration of intracellular thiol levels modulates the cytotoxic effects of different NO donors and lipopolysaccharide-induced NO in the murine macrophage cell lin J774A.1. The NO-releasing compound S-nitroso-N-acetylpenicillamine caused a significant concentration-dependent loss of viability of the macrophages only under glucose-limiting conditions. The cytotoxic effect of S-nitroso-N-acetylpenicillamine was prevented by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO). Depletion of total glutathione before exposure to S-nitroso-N-acetylpenicillamine further decrease cell viability while pretreatment with N-acetylcysteine was protective. Comparing equimolar concentrations of various NO donors including S-nitrosoglutathione, S-nitrosocysteine and 3-morpholino-sydnonimine hydrochloride, cytotoxicity appeared to be related to the relative stability of the test compound. Both the order of stability and the order of potency for cell killing was S-nitrosoglutathione > S-nitroso-N-acetylpenicillamine > S-nitrosocysteine = 3-morpholino-sydnonimine hydrochloride. Stimulation of the macrophages with lipopolysaccharide and interferon-gamma resulted in dose-dependent cell injury and NO production. Glutathione depletion prior to stimulation considerably decreased macrophage viability as well as the NO production. In contrast to the protective effect on S-nitroso-N-acetylpenicillamine-mediated injury, pretreatment with N-acetylcysteine did not influence the lipopolysaccharide-mediated cytotoxicity. These results demonstrate that (a) reduction in the availability of glucose and intracellular glutathione renders the cells more vulnerable to the cytotoxic effects of NO donors, (b) in this model of cytotoxicity, long-lived NO donors were more cytotoxic than short-lived NO donors, (c) the differential effects of N-acetylcysteine on S-nitroso-N-acetylpenicillamine-induced and bacterial lipopolysaccharide-mediated cytotoxicity support the existence of other toxic species different from NO or NO-related compounds with a potent cytotoxic activity in immunostimulated macrophages, and (d) other non-protein thiols like N-acetylcysteine may substitute for glutathione as a major component of the cellular antioxidant defense system.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Zamora R,Matthys KE,Herman AGdoi
10.1016/s0014-2999(96)00918-1subject
Has Abstractpub_date
1997-02-19 00:00:00pages
87-96issue
1eissn
0014-2999issn
1879-0712pii
S0014299996009181journal_volume
321pub_type
杂志文章abstract::Effects of ouabain on force of contraction were compared in electrically driven isolated tissue preparations of guinea-pig left atria and diaphragm. A distinct and steady positive inotropic effect of ouabain was observed in atrial preparations, whereas in diaphragm preparations, ouabain produced only a slight and tran...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90188-6
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abstract::Exposure to cold (4 degrees C) of catheterized rats acclimated to 20 degrees C resulted in a progressive increase in plasma noradrenaline (NA) concentrations which reached values consistently more than twice the basal ones (20 degrees C) by about 30 min. No further increase in plasma NA levels were detected when the c...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90478-7
更新日期:1981-01-29 00:00:00
abstract::TL-99 and 3-PPP, two putative dopamine autoreceptor agonists, effectively suppressed serum prolactin (PRL) concentrations in rats treated with alpha-methyltyrosine. In addition, the secretion of PRL from anterior pituitary tissue under in vitro conditions was significantly inhibited by TL-99 and 3-PPP. These findings ...
journal_title:European journal of pharmacology
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doi:10.1016/0014-2999(83)90565-4
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abstract::The role of dopamine transmission on striatal acetylcholine release was investigated by using brain microdialysis. Blockade of dopamine D2 receptors with (-)-sulpiride or haloperidol increased acetylcholine release to a maximum of 80% (after 50 and 0.5 mg/kg, respectively). This effect was prevented by blockade of dop...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90409-x
更新日期:1994-01-14 00:00:00
abstract::The administration of ethyl beta-carboline-3-carboxylate (beta-CCE), a ligand for benzodiazepine receptors, did not affect the cerebellar cyclic GMP level in mice, but giving beta-CCE together with diazepam significantly inhibited the diazepam-induced decrease in cyclic GMP. The fact that no antagonism was observed wh...
journal_title:European journal of pharmacology
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doi:10.1016/0014-2999(82)90065-6
更新日期:1982-05-21 00:00:00
abstract::KCl-contracted aortic rings from 18-month-old rats, in contrast with those from 2-month-old rats, showed a substantial reduction in the relaxant effects of the non-selective beta-adrenoceptor agonist, isoproterenol, and of the selective beta 2-adrenoceptor agonist, clenbuterol, without changes in the relaxant actions ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90618-z
更新日期:1991-06-06 00:00:00
abstract::Experiments were conducted to explore the effects of Neuropeptide FF acting at spinal and supraspinal sites in models of chronic inflammatory or neuropathic pain and of acute pain. Neuropeptide FF was administered intrathecally (i.t.; 10.0, 25.0 and 50.0 nmol) or intracerebroventricularly (i.c.v.; 10.0, 12.5 and 15.0 ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00668-3
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abstract::The aim of this work was to investigate the effect of P-glycoprotein modulators on human extraneuronal monoamine transporter (EMT)-mediated transport. The experiments were performed using a cell line from human embryonic kidney (HEK293 cells) stably transfected with pcDNA3hEMT (293(hEMT)), or with pcDNA3 alone (293(co...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01055-x
更新日期:2001-06-22 00:00:00
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00664-s
更新日期:1995-01-05 00:00:00
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90018-x
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172630
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90053-1
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.09.020
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00639-7
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(76)90264-8
更新日期:1976-03-01 00:00:00
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journal_title:European journal of pharmacology
pub_type: 杂志文章
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