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

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-dibutyrate, did not develop acute tolerance. Regarding activation of protein kinase C, regular exposure to 70% N(2)O 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(2)O 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(2)O. These results suggest that brain protein kinase C negatively regulates the antinociceptive effect of N(2)O, and that activation of brain protein kinase C is related to the development of acute tolerance to N(2)O-induced antinociception in mice.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Ishikawa M,Matsushita Y,Abe K,Utsunomiya I,Hoshi K,Quock RM,Taguchi K

doi

10.1016/j.neuroscience.2006.02.001

keywords:

subject

Has Abstract

pub_date

2006-06-19 00:00:00

pages

227-33

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(06)00188-6

journal_volume

140

pub_type

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