<scp>l</scp>‐Arginine exerts a dual role in nociceptive processing in the brain: involvement of the kyotorphin‐Met‐enkephalin pathway and NO‐cyclic GMP pathway

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書誌事項

公開日
1993-05
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1111/j.1476-5381.1993.tb13533.x
公開者
Wiley

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<jats:p><jats:list list-type="explicit-label"> <jats:list-item><jats:p>Intracerebroventricular (i.c.v.) administration of <jats:sc>l</jats:sc>‐arginine (<jats:sc>l</jats:sc>‐Arg), at 10–100 μg per mouse, produced antinociception in mice, as assessed by the tail flick test; this antinociception was reversed by pretreatment (s.c.) with naltrindole (NTI), a δ‐selective opioid antagonist, and by co‐administered <jats:sc>l</jats:sc>‐leucyl‐<jats:sc>l</jats:sc>‐arginine (Leu‐Arg), a kyotorphin (endogenous Met‐enkephalin releaser) receptor antagonist.</jats:p></jats:list-item> <jats:list-item><jats:p><jats:sc>l</jats:sc>‐N<jats:sup>G</jats:sup>‐nitroarginine methyl ester (<jats:sc>l</jats:sc>‐NAME), a NO synthase inhibitor, but not <jats:sc>d</jats:sc>‐N<jats:sup>G</jats:sup>‐nitroarginine methyl ester, given i.c.v. at 3–10 μg per mouse, exhibited antinociceptive activity that was resistant to naloxone (s.c.), NTI (s.c.) and Leu‐Arg (i.c.v.).</jats:p></jats:list-item> <jats:list-item><jats:p>The <jats:sc>l</jats:sc>‐NAME (i.c.v.)‐induced antinociception was not reversed by <jats:sc>l</jats:sc>‐Arg (i.c.v.), which was antinociceptive by itself, but was abolished by combined injection of <jats:sc>l</jats:sc>‐Arg plus Leu‐Arg (i.c.v.) or by <jats:sc>l</jats:sc>‐Arg (i.c.v.) after NTI (s.c.).</jats:p></jats:list-item> <jats:list-item><jats:p>Methylene blue (MB), a soluble guanylate cyclase inhibitor, at 0.1–1 μg per mouse, produced antinociception by i.c.v. administration. The antinociception induced by MB (i.c.v.) or <jats:sc>l</jats:sc>‐NAME (i.c.v.) was reversed by co‐administered dibutyryl cyclic GMP.</jats:p></jats:list-item> <jats:list-item><jats:p>These findings suggest that <jats:sc>l</jats:sc>‐Arg plays a dual role in nociceptive processing in the brain, being antinociceptive via the kyotorphin‐Met‐enkephalin pathway and nociceptive via the NO‐cyclic GMP pathway.</jats:p></jats:list-item> </jats:list></jats:p>

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