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A comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

A comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis. / Nielsen, O H; Ahnfelt-Rønne, I; Elmgreen, J.

I: Pharmacology & Toxicology, Bind 62, Nr. 5, 05.1988, s. 322-5.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Nielsen, OH, Ahnfelt-Rønne, I & Elmgreen, J 1988, 'A comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis', Pharmacology & Toxicology, bind 62, nr. 5, s. 322-5.

APA

Nielsen, O. H., Ahnfelt-Rønne, I., & Elmgreen, J. (1988). A comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis. Pharmacology & Toxicology, 62(5), 322-5.

Vancouver

Nielsen OH, Ahnfelt-Rønne I, Elmgreen J. A comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis. Pharmacology & Toxicology. 1988 maj;62(5):322-5.

Author

Nielsen, O H ; Ahnfelt-Rønne, I ; Elmgreen, J. / A comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis. I: Pharmacology & Toxicology. 1988 ; Bind 62, Nr. 5. s. 322-5.

Bibtex

@article{e8ca5d76697a4a33b710885e71242d0b,
title = "A comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis",
abstract = "The effect of timegadine, a novel experimental antirheumatic drug, on human neutrophil (PMN) 5-lipoxygenase activity and leukotriene B4 (LTB4) chemotaxis was compared with that of two second-line antiinflammatory drugs, D-penicillamine and levamisole. 1-14C-Arachidonic acid (AA) was incorporated into the purified cells until steady state conditions were obtained. After preincubation with serial dilutions of the three drugs, AA release and metabolism was stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thin-layer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxis of PMNs towards LTB4 was measured in a modified Boyden chamber. Timegadine showed dose-dependent inhibition of both the 5-lipoxygenase pathway (IC50 3.4 x 10(-5) M), and of chemotaxis (IC50 3 x 10(-4) M). Inhibition of the release of AA from phospholipids, however, occurred only at therapeutically irrelevant doses (millimolar concentrations). Levamisole and D-penicillamine did not inhibit any of the cell functions investigated. Inhibition of both neutrophil motility and cellular synthesis of pro-inflammatory eicosanoids, may thus contribute to the clinical effects of timegadine in rheumatoid arthritis.",
keywords = "Anti-Inflammatory Agents, Non-Steroidal/pharmacology, Arachidonate 15-Lipoxygenase/metabolism, Arachidonic Acid, Arachidonic Acids/metabolism, Chemotaxis, Leukocyte/drug effects, Guanidines/pharmacology, Humans, In Vitro Techniques, Leukotriene B4/metabolism, Levamisole/pharmacology, Neutrophils/drug effects, Penicillamine/pharmacology",
author = "Nielsen, {O H} and I Ahnfelt-R{\o}nne and J Elmgreen",
year = "1988",
month = "5",
language = "English",
volume = "62",
pages = "322--5",
journal = "Pharmacology and Toxicology",
issn = "0901-9928",
publisher = "Munksgaard",
number = "5",

}

RIS

TY - JOUR

T1 - A comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis

AU - Nielsen, O H

AU - Ahnfelt-Rønne, I

AU - Elmgreen, J

PY - 1988/5

Y1 - 1988/5

N2 - The effect of timegadine, a novel experimental antirheumatic drug, on human neutrophil (PMN) 5-lipoxygenase activity and leukotriene B4 (LTB4) chemotaxis was compared with that of two second-line antiinflammatory drugs, D-penicillamine and levamisole. 1-14C-Arachidonic acid (AA) was incorporated into the purified cells until steady state conditions were obtained. After preincubation with serial dilutions of the three drugs, AA release and metabolism was stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thin-layer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxis of PMNs towards LTB4 was measured in a modified Boyden chamber. Timegadine showed dose-dependent inhibition of both the 5-lipoxygenase pathway (IC50 3.4 x 10(-5) M), and of chemotaxis (IC50 3 x 10(-4) M). Inhibition of the release of AA from phospholipids, however, occurred only at therapeutically irrelevant doses (millimolar concentrations). Levamisole and D-penicillamine did not inhibit any of the cell functions investigated. Inhibition of both neutrophil motility and cellular synthesis of pro-inflammatory eicosanoids, may thus contribute to the clinical effects of timegadine in rheumatoid arthritis.

AB - The effect of timegadine, a novel experimental antirheumatic drug, on human neutrophil (PMN) 5-lipoxygenase activity and leukotriene B4 (LTB4) chemotaxis was compared with that of two second-line antiinflammatory drugs, D-penicillamine and levamisole. 1-14C-Arachidonic acid (AA) was incorporated into the purified cells until steady state conditions were obtained. After preincubation with serial dilutions of the three drugs, AA release and metabolism was stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thin-layer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxis of PMNs towards LTB4 was measured in a modified Boyden chamber. Timegadine showed dose-dependent inhibition of both the 5-lipoxygenase pathway (IC50 3.4 x 10(-5) M), and of chemotaxis (IC50 3 x 10(-4) M). Inhibition of the release of AA from phospholipids, however, occurred only at therapeutically irrelevant doses (millimolar concentrations). Levamisole and D-penicillamine did not inhibit any of the cell functions investigated. Inhibition of both neutrophil motility and cellular synthesis of pro-inflammatory eicosanoids, may thus contribute to the clinical effects of timegadine in rheumatoid arthritis.

KW - Anti-Inflammatory Agents, Non-Steroidal/pharmacology

KW - Arachidonate 15-Lipoxygenase/metabolism

KW - Arachidonic Acid

KW - Arachidonic Acids/metabolism

KW - Chemotaxis, Leukocyte/drug effects

KW - Guanidines/pharmacology

KW - Humans

KW - In Vitro Techniques

KW - Leukotriene B4/metabolism

KW - Levamisole/pharmacology

KW - Neutrophils/drug effects

KW - Penicillamine/pharmacology

M3 - Journal article

C2 - 2842744

VL - 62

SP - 322

EP - 325

JO - Pharmacology and Toxicology

JF - Pharmacology and Toxicology

SN - 0901-9928

IS - 5

ER -

ID: 218729085