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The antipyretic eff...
The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1–mediated hypothermia and is associated with prostaglandin inhibition in the brain
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- Mirrasekhian, Elahe, 1978- (författare)
- Linköpings universitet,Linköping University,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Nilsson, Johan L.A. (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, Lund, Sweden
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- Shionoya, Kiseko, 1964- (författare)
- Linköpings universitet,Linköping University,Avdelning för neurobiologi,Medicinska fakulteten
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- Blomgren, Anders (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, Lund, Sweden
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- Zygmunt, Peter M. (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund, Sweden
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- Engblom, David, 1975- (författare)
- Linköpings universitet,Linköping University,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Högestätt, Edward D. (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, Lund, Sweden
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- Blomqvist, Anders, 1949- (författare)
- Linköpings universitet,Linköping University,Avdelning för neurobiologi,Medicinska fakulteten
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(creator_code:org_t)
- Federation of American Societies for Experimental Biology, 2018
- 2018
- Engelska 9 s.
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Ingår i: FASEB Journal. - : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 32:10, s. 5751-5759
- Relaterad länk:
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http://dx.doi.org/10...
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https://liu.diva-por... (primary) (Raw object)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- The mode of action of paracetamol (acetaminophen), which is widely used for treating pain and fever, has remained obscure, but may involve several distinct mechanisms, including cyclooxygenase inhibition and transient receptor potential ankyrin 1 (TRPA1) channel activation, the latter being recently associated with paracetamol’s propensity to elicit hypothermia at higher doses. Here, we examined whether the antipyretic effect of paracetamol was due to TRPA1 activation or cyclooxygenase inhibition. Treatment of wild-type and TRPA1 knockout mice rendered febrile by immune challenge with LPS with a dose of paracetamol that did not produce hypothermia (150 mg/kg) but is known to be analgetic, abolished fever in both genotypes. Paracetamol completely suppressed the LPS-induced elevation of prostaglandin E2 in the brain and also reduced the levels of several other prostanoids. The hypothermia induced by paracetamol was abolished in mice treated with the electrophile-scavenger N-acetyl cysteine. We conclude that paracetamol’s antipyretic effect in mice is dependent on inhibition of cyclooxygenase activity, including the formation of pyrogenic prostaglandin E2, whereas paracetamol-induced hypothermia likely is mediated by the activation of TRPA1 by electrophilic metabolites of paracetamol, similar to its analgesic effect in some experimental paradigms.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Acetaminophen
- Fever
- N-acetyl cysteine
- NAPQI
- TRPA1
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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