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. 1992 Dec;107(4):1096–1101. doi: 10.1111/j.1476-5381.1992.tb13413.x

L-leucyl-L-arginine, naltrindole and D-arginine block antinociception elicited by L-arginine in mice with carrageenin-induced hyperalgesia.

A Kawabata 1, Y Nishimura 1, H Takagi 1
PMCID: PMC1907944  PMID: 1467831

Abstract

1. Intraplantar injection of carrageenin into the mouse hind paw produced hyperalgesia when measured by the paw pressure test (Randall & Selitto method). 2. Subcutaneous administration of L-arginine (100-1,000 mg kg-1), a possible precursor of kyotorphin which is an endogenous analgesic neuropeptide, inhibited carrageenin-induced hyperalgesia in a dose-dependent manner. This effect was blocked by subcutaneous administration of naloxone, naltrindole, a selective delta-opioid receptor antagonist (enkephalin antagonist), and D-arginine. 3. Intracerebroventricular administration of L-leucyl-L-arginine inhibited the antinociceptive effect of systemically administered L-arginine in hyperalgesic mice. 4. Intracerebroventricular administration of L-arginine (3 and 30 micrograms per mouse) and kyotorphin (300 ng-3 micrograms per mouse) produced antinociception in hyperalgesic mice. The antinociceptive effects of L-arginine but not kyotorphin were blocked by intracerebroventricular administration of D-arginine. 5. These results suggest that L-arginine-induced antinociception is mediated by activation of 'kyotorphinergic' nerves followed by activation of the 'opioidergic' (possible 'enkephalinergic') nerves in the central nervous system.

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Selected References

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  1. Bredt D. S., Snyder S. H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682–685. doi: 10.1073/pnas.87.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Coderre T. J., Melzack R. Central neural mediators of secondary hyperalgesia following heat injury in rats: neuropeptides and excitatory amino acids. Neurosci Lett. 1991 Sep 30;131(1):71–74. doi: 10.1016/0304-3940(91)90339-u. [DOI] [PubMed] [Google Scholar]
  3. Coderre T. J., Melzack R. Cutaneous hyperalgesia: contributions of the peripheral and central nervous systems to the increase in pain sensitivity after injury. Brain Res. 1987 Feb 24;404(1-2):95–106. doi: 10.1016/0006-8993(87)91359-x. [DOI] [PubMed] [Google Scholar]
  4. Coderre T. J., Melzack R. Increased pain sensitivity following heat injury involves a central mechanism. Behav Brain Res. 1985 May;15(3):259–262. doi: 10.1016/0166-4328(85)90181-0. [DOI] [PubMed] [Google Scholar]
  5. Durate I. D., Lorenzetti B. B., Ferreira S. H. Peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway. Eur J Pharmacol. 1990 Sep 21;186(2-3):289–293. doi: 10.1016/0014-2999(90)90446-d. [DOI] [PubMed] [Google Scholar]
  6. Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Regional haemodynamic changes during oral ingestion of NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats. Br J Pharmacol. 1990 Sep;101(1):10–12. doi: 10.1111/j.1476-5381.1990.tb12079.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Haley J. E., Dickenson A. H., Schachter M. Electrophysiological evidence for a role of nitric oxide in prolonged chemical nociception in the rat. Neuropharmacology. 1992 Mar;31(3):251–258. doi: 10.1016/0028-3908(92)90175-o. [DOI] [PubMed] [Google Scholar]
  8. Hargreaves K. M., Troullos E. S., Dionne R. A., Schmidt E. A., Schafer S. C., Joris J. L. Bradykinin is increased during acute and chronic inflammation: therapeutic implications. Clin Pharmacol Ther. 1988 Dec;44(6):613–621. doi: 10.1038/clpt.1988.202. [DOI] [PubMed] [Google Scholar]
  9. Harima A., Shimizu H., Takagi H. Analgesic effect of L-arginine in patients with persistent pain. Eur Neuropsychopharmacol. 1991 Dec;1(4):529–533. doi: 10.1016/0924-977x(91)90006-g. [DOI] [PubMed] [Google Scholar]
  10. Hughes S. R., Williams T. J., Brain S. D. Evidence that endogenous nitric oxide modulates oedema formation induced by substance P. Eur J Pharmacol. 1990 Dec 4;191(3):481–484. doi: 10.1016/0014-2999(90)94184-y. [DOI] [PubMed] [Google Scholar]
  11. Ialenti A., Ianaro A., Moncada S., Di Rosa M. Modulation of acute inflammation by endogenous nitric oxide. Eur J Pharmacol. 1992 Feb 11;211(2):177–182. doi: 10.1016/0014-2999(92)90526-a. [DOI] [PubMed] [Google Scholar]
  12. Kawabata A., Fukuzumi Y., Fukushima Y., Takagi H. Antinociceptive effect of L-arginine on the carrageenin-induced hyperalgesia of the rat: possible involvement of central opioidergic systems. Eur J Pharmacol. 1992 Jul 21;218(1):153–158. doi: 10.1016/0014-2999(92)90159-2. [DOI] [PubMed] [Google Scholar]
  13. Kayser V., Guilbaud G. Local and remote modifications of nociceptive sensitivity during carrageenin-induced inflammation in the rat. Pain. 1987 Jan;28(1):99–107. doi: 10.1016/0304-3959(87)91064-5. [DOI] [PubMed] [Google Scholar]
  14. Kitahata L. M. Modes and sites of "analgesic" action of anesthetics on the spinal cord. Int Anesthesiol Clin. 1975 Spring;13(1):149–170. doi: 10.1097/00004311-197513010-00007. [DOI] [PubMed] [Google Scholar]
  15. Levi G., Kandera J., Lajtha A. Control of cerebral metabolite levels. I. Amino acid uptake and levels in various species. Arch Biochem Biophys. 1967 Mar;119(1):303–311. doi: 10.1016/0003-9861(67)90460-2. [DOI] [PubMed] [Google Scholar]
  16. Levy L. Carrageenan paw edema in the mouse. Life Sci. 1969 Jun 1;8(11):601–606. doi: 10.1016/0024-3205(69)90021-6. [DOI] [PubMed] [Google Scholar]
  17. Mollace V., De Francesco E. A., Nisticó G. Evidence that pharmacological manipulations of central L-arginine-NO pathway influence blood pressure and heart rate in rats. Neurosci Lett. 1992 Mar 16;137(1):87–90. doi: 10.1016/0304-3940(92)90305-q. [DOI] [PubMed] [Google Scholar]
  18. Moore P. K., Oluyomi A. O., Babbedge R. C., Wallace P., Hart S. L. L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse. Br J Pharmacol. 1991 Jan;102(1):198–202. doi: 10.1111/j.1476-5381.1991.tb12153.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Portoghese P. S., Sultana M., Takemori A. E. Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist. Eur J Pharmacol. 1988 Jan 27;146(1):185–186. doi: 10.1016/0014-2999(88)90502-x. [DOI] [PubMed] [Google Scholar]
  20. RANDALL L. O., SELITTO J. J. A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther. 1957 Sep 1;111(4):409–419. [PubMed] [Google Scholar]
  21. Takagi H., Shiomi H., Ueda H., Amano H. A novel analgesic dipeptide from bovine brain is a possible Met-enkephalin releaser. Nature. 1979 Nov 22;282(5737):410–412. doi: 10.1038/282410a0. [DOI] [PubMed] [Google Scholar]
  22. Takagi H., Shiomi H., Ueda H., Amano H. Morphine-like analgesia by a new dipeptide, L-tyrosyl-L-arginine (Kyotorphin) and its analogue. Eur J Pharmacol. 1979 Apr 1;55(1):109–111. doi: 10.1016/0014-2999(79)90154-7. [DOI] [PubMed] [Google Scholar]
  23. Treede R. D., Meyer R. A., Raja S. N., Campbell J. N. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol. 1992;38(4):397–421. doi: 10.1016/0301-0082(92)90027-c. [DOI] [PubMed] [Google Scholar]
  24. Ueda H., Matsumoto S., Yoshihara Y., Fukushima N., Takagi H. Uptake and release of kyotorphin in rat brain synaptosomes. Life Sci. 1986 Jun 30;38(26):2405–2411. doi: 10.1016/0024-3205(86)90609-0. [DOI] [PubMed] [Google Scholar]
  25. Ueda H., Ming G., Hazato T., Katayama T., Takagi H. Degradation of kyotorphin by a purified membrane-bound-aminopeptidase from monkey brain: potentiation of kyotorphin-induced analgesia by a highly effective inhibitor, bestatin. Life Sci. 1985 May 13;36(19):1865–1871. doi: 10.1016/0024-3205(85)90160-2. [DOI] [PubMed] [Google Scholar]
  26. Ueda H., Tatsumi K., Shiomi H., Takagi H. Analgesic dipeptide, kyotorphin (Tyr-Arg), is highly concentrated in the synaptosomal fraction of the rat brain. Brain Res. 1982 Jan 7;231(1):222–224. doi: 10.1016/0006-8993(82)90023-3. [DOI] [PubMed] [Google Scholar]
  27. Ueda H., Yoshihara Y., Fukushima N., Shiomi H., Nakamura A., Takagi H. Kyotorphin (tyrosine-arginine) synthetase in rat brain synaptosomes. J Biol Chem. 1987 Jun 15;262(17):8165–8173. [PubMed] [Google Scholar]
  28. Ueda H., Yoshihara Y., Misawa H., Fukushima N., Katada T., Ui M., Takagi H., Satoh M. The kyotorphin (tyrosine-arginine) receptor and a selective reconstitution with purified Gi, measured with GTPase and phospholipase C assays. J Biol Chem. 1989 Mar 5;264(7):3732–3741. [PubMed] [Google Scholar]
  29. Yoshihara Y., Ueda H., Imajoh S., Takagi H., Satoh M. Calcium-activated neutral protease (CANP), a putative processing enzyme of the neuropeptide, kyotorphin, in the brain. Biochem Biophys Res Commun. 1988 Sep 15;155(2):546–553. doi: 10.1016/s0006-291x(88)80529-1. [DOI] [PubMed] [Google Scholar]

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