Journal article
Involvement of brain protein kinase C in nitrous oxide-induced antinociception in mice
Neuroscience, Vol.140(1), pp.227-233
2006
Handle:
https://hdl.handle.net/2376/102000
PMID: 16533570
Abstract
Exposure of mice to the anesthetic gas nitrous oxide (N
2O) produces a marked antinociceptive effect. Protein kinase C is a key regulatory enzyme that may be targeted by general anesthetics. However, a relationship between N
2O-induced antinociception and protein kinase C has yet to be established. The present study was conducted to identify whether protein kinase C might influence N
2O-induced antinociception in mice. Regular exposure (11 min) to N
2O produced concentration-dependent antinociception in mice, as determined using the abdominal constriction test. N
2O-induced antinociception was attenuated by i.c.v. pretreatment with phorbol 12,13-dibutyrate, a protein kinase C activator. This phorbol 12,13-dibutyrate antagonism of N
2O-induced antinociception was reversed by i.c.v. pretreatment with calphostin C, a protein kinase C inhibitor. Long-term exposure (41 min in total, including 30 min prior to, and 11 min of analgesic testing) to 70% N
2O produced reduced analgesic effects, compared with regular exposure to 70% N
2O, thus indicating acute tolerance to N
2O-induced antinociception. However, mice pretreated with calphostin C, chelerythrine, which is another protein kinase C inhibitor, and phorbol 12,13-dibutyrate, did not develop acute tolerance. Regarding activation of protein kinase C, regular exposure to 70% N
2O did not increase protein kinase C within the membrane fraction of brain tissue, as determined by immunoblot analysis, but long-term exposure to 70% N
2O did. The i.c.v. pretreatment with calphostin C and phorbol 12,13-dibutyrate prevented the increase in protein kinase C observed with long-term exposure to 70% N
2O. These results suggest that brain protein kinase C negatively regulates the antinociceptive effect of N
2O, and that activation of brain protein kinase C is related to the development of acute tolerance to N
2O-induced antinociception in mice.
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Details
- Title
- Involvement of brain protein kinase C in nitrous oxide-induced antinociception in mice
- Creators
- M Ishikawa - Department of Pharmacotherapeutics, Showa Pharmaceutical University, P.O. Box 3-3165, Higashitamagawagakuen, Tokyo 194-8543, JapanY Matsushita - Department of Pharmacotherapeutics, Showa Pharmaceutical University, P.O. Box 3-3165, Higashitamagawagakuen, Tokyo 194-8543, JapanK Abe - Department of Pharmacotherapeutics, Showa Pharmaceutical University, P.O. Box 3-3165, Higashitamagawagakuen, Tokyo 194-8543, JapanI Utsunomiya - Department of Pharmacotherapeutics, Showa Pharmaceutical University, P.O. Box 3-3165, Higashitamagawagakuen, Tokyo 194-8543, JapanK Hoshi - Department of Pharmacotherapeutics, Showa Pharmaceutical University, P.O. Box 3-3165, Higashitamagawagakuen, Tokyo 194-8543, JapanR.M Quock - Department of Pharmaceutical Sciences, College of Pharmacy, and Center for Integrative Biotechnology, Washington State University, Pullman, WA, USAK Taguchi - Department of Pharmacotherapeutics, Showa Pharmaceutical University, P.O. Box 3-3165, Higashitamagawagakuen, Tokyo 194-8543, Japan
- Publication Details
- Neuroscience, Vol.140(1), pp.227-233
- Academic Unit
- Psychology, Department of
- Publisher
- Elsevier Ltd
- Identifiers
- 99900546795801842
- Language
- English
- Resource Type
- Journal article