Involvement of brain protein kinase C in nitrous oxide-induced antinociception in mice

Neuroscience
M IshikawaK Taguchi

Abstract

Exposure of mice to the anesthetic gas nitrous oxide (N(2)O) 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(2)O-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(2)O-induced antinociception in mice. Regular exposure (11 min) to N(2)O produced concentration-dependent antinociception in mice, as determined using the abdominal constriction test. N(2)O-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(2)O-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(2)O produced reduced analgesic effects, compared with regular exposure to 70% N(2)O, thus indicating acute tolerance to N(2)O-induced antinociception. However, mice pretreated with calphostin C, chelerythrine, which is another protein kinase C inhibitor, and phorbol 12,13-dibutyra...Continue Reading

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