Article date: May 1993
By: Atsufumi Kawabata, Nahoko Umeda, Hiroshi Takagi, in Volume 109, Issue 1, pages 73-79
Intracerebroventricular (i.c.v.) administration of l‐arginine (l‐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 l‐leucyl‐l‐arginine (Leu‐Arg), a kyotorphin (endogenous Met‐enkephalin releaser) receptor antagonist.
l‐NG‐nitroarginine methyl ester (l‐NAME), a NO synthase inhibitor, but not d‐NG‐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.).
The l‐NAME (i.c.v.)‐induced antinociception was not reversed by l‐Arg (i.c.v.), which was antinociceptive by itself, but was abolished by combined injection of l‐Arg plus Leu‐Arg (i.c.v.) or by l‐Arg (i.c.v.) after NTI (s.c.).
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 l‐NAME (i.c.v.) was reversed by co‐administered dibutyryl cyclic GMP.
These findings suggest that l‐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.
Intracerebroventricular (i.c.v.) administration of l‐arginine (l‐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 l‐leucyl‐l‐arginine (Leu‐Arg), a kyotorphin (endogenous Met‐enkephalin releaser) receptor antagonist.
l‐NG‐nitroarginine methyl ester (l‐NAME), a NO synthase inhibitor, but not d‐NG‐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.).
The l‐NAME (i.c.v.)‐induced antinociception was not reversed by l‐Arg (i.c.v.), which was antinociceptive by itself, but was abolished by combined injection of l‐Arg plus Leu‐Arg (i.c.v.) or by l‐Arg (i.c.v.) after NTI (s.c.).
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 l‐NAME (i.c.v.) was reversed by co‐administered dibutyryl cyclic GMP.
These findings suggest that l‐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.
DOI: 10.1111/j.1476-5381.1993.tb13533.x
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