Abstract | OBJECTIVE: MATERIALS AND METHODS: The time course of iNOS mRNA expression in rat spinal cord and inflamed paw was assessed by means of quantitative real time RT-PCR. In addition, the effects of the iNOS inhibitor L-NIL on inflammatory paw edema and thermal hyperalgesia were studied in comparison to those of the NO-donor RE-2047. L-NIL (3, 9, 27 and 81 mg/kg) and RE-2047 (3, 9 and 27 mg/kg) or vehicle were administered orally 15 min prior to the intraplantar injection of 0.625 mg zymosan. RESULTS: Following zymosan injection, mRNA expression of iNOS increased in the inflamed paw and spinal cord with a maximum at 2.5 and 4 h, respectively. In the spinal cord iNOS mRNA started to decline at 10 h whereas it remained at maximum in the inflamed paw up to the end of the observation period of 24 h. As expected, RE-2047 had significant pronociceptive and proinflammatory effects. L-NIL significantly reduced paw inflammation at 27 and 81 mg/kg but failed to reduce hyperalgesia at the doses tested. CONCLUSIONS: The results show that iNOS is upregulated in the inflamed tissue and spinal cord with a similar time course. The effects obtained with L-NIL suggest that iNOS differently contributes to the inflammatory and nociceptive response induced by zymosan.
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Authors | H Gühring, I Tegeder, J Lötsch, A Pahl, U Werner, P W Reeh, K Rehse, K Brune, G Geisslinger |
Journal | Inflammation research : official journal of the European Histamine Research Society ... [et al.]
(Inflamm Res)
Vol. 50
Issue 2
Pg. 83-8
(Feb 2001)
ISSN: 1023-3830 [Print] Switzerland |
PMID | 11289658
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3-methylsydnone-5-nitrosimine
- Enzyme Inhibitors
- N(6)-(1-iminoethyl)lysine
- Nitric Oxide Donors
- RNA, Messenger
- Sydnones
- Nitric Oxide
- Zymosan
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nos2 protein, rat
- Lysine
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Topics |
- Animals
- Enzyme Inhibitors
(pharmacology)
- Foot
- Hot Temperature
- Hyperalgesia
(enzymology, etiology)
- Inflammation
(chemically induced, enzymology)
- Kinetics
- Lysine
(analogs & derivatives, pharmacokinetics, pharmacology)
- Male
- Nitric Oxide
(physiology)
- Nitric Oxide Donors
(pharmacology)
- Nitric Oxide Synthase
(antagonists & inhibitors, genetics)
- Nitric Oxide Synthase Type II
- RNA, Messenger
(analysis)
- Rats
- Rats, Sprague-Dawley
- Spinal Cord
(chemistry)
- Sydnones
(pharmacology)
- Zymosan
(administration & dosage)
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