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. 1996 Oct;39(4):539–544. doi: 10.1136/gut.39.4.539

L-Arginine, nitric oxide, and intestinal secretion: studies in rat jejunum in vivo.

F H Mourad 1, L J O'Donnell 1, E A Andre 1, C P Bearcroft 1, R A Owen 1, M L Clark 1, M J Farthing 1
PMCID: PMC1383266  PMID: 8944562

Abstract

BACKGROUND: L-Arginine has been shown to induce fluid secretion in human jejunum. Nitric oxide, a derivative of L-arginine is thought to have an important role as an intestinal secretagogue. AIM: To determine the effect of L-arginine and the nitric oxide synthase inhibitor, nitro L-arginine methyl ester (L-NAME), on fluid and electrolyte movement in rat jejunum. METHODS: A 25 cm segment of rat jejunum was perfused in situ with iso-osmotic solutions containing either (1) saline, (2) D-arginine 20, (3) L-arginine 20, (4) L-NAME 0.1, 1, or 20 mmol/l, or (5) a combination of L-arginine 20 and L-NAME 0.1, 1, or 20 mmol/l. In further groups the effect of a subcutaneous injection of L-NAME 100 mg/kg was examined in rats pretreated with either D-or L-arginine 500 mg/kg. RESULTS: L-Arginine, unlike D-arginine, induced fluid secretion despite being better absorbed (mean -7.3 v 17.0 microliters/min/g; p < 0.01). L-NAME at 0.1 mmol/l had no effect on basal fluid movement but reversed L-arginine induced secretion (7.8; p < 0.05). L-NAME at 1 and 20 mmol/l induced fluid secretion (-15.4 and -28.4, respectively), which was enhanced by the addition of L-arginine (-30.0 and -41.0, respectively; both p < 0.05). A subcutaneous injection of L-NAME resulted in marked fluid secretion (-39.9) and histological evidence of intestinal ischaemia. These changes were attenuated or reversed by pretreatment with subcutaneous L- but not D-arginine. CONCLUSIONS: L-arginine induces intestinal fluid secretion through production of nitric oxide. There is a delicate balance between the effect of nitric oxide as a secretagogue and its effect on maintaining blood flow and thus preventing intestinal ischaemia.

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Selected References

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  1. Adibi S. A. Leucine absorption rate and net movements of sodium and water in human jejunum. J Appl Physiol. 1970 Jun;28(6):753–757. doi: 10.1152/jappl.1970.28.6.753. [DOI] [PubMed] [Google Scholar]
  2. Bern M. J., Sturbaum C. W., Karayalcin S. S., Berschneider H. M., Wachsman J. T., Powell D. W. Immune system control of rat and rabbit colonic electrolyte transport. Role of prostaglandins and enteric nervous system. J Clin Invest. 1989 Jun;83(6):1810–1820. doi: 10.1172/JCI114086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buxton I. L., Cheek D. J., Eckman D., Westfall D. P., Sanders K. M., Keef K. D. NG-nitro L-arginine methyl ester and other alkyl esters of arginine are muscarinic receptor antagonists. Circ Res. 1993 Feb;72(2):387–395. doi: 10.1161/01.res.72.2.387. [DOI] [PubMed] [Google Scholar]
  4. Field M., Graf L. H., Jr, Laird W. J., Smith P. L. Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2800–2804. doi: 10.1073/pnas.75.6.2800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Hegarty J. E., Fairclough P. D., Clark M. L., Dawson A. M. Jejunal water and electrolyte secretion induced by L-arginine in man. Gut. 1981 Feb;22(2):108–113. doi: 10.1136/gut.22.2.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hellier M. D., Thirumalai C., Holdsworth C. D. The effect of amino acids and dipeptides on sodium and water absorption in man. Gut. 1973 Jan;14(1):41–45. doi: 10.1136/gut.14.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. IZUMI Y. NEW SAKAGUCHI REACTION. Anal Biochem. 1965 Feb;10:218–226. doi: 10.1016/0003-2697(65)90262-9. [DOI] [PubMed] [Google Scholar]
  9. Izzo A. A., Gaginella T. S., Mascolo N., Capasso F. Nitric oxide as a mediator of the laxative action of magnesium sulphate. Br J Pharmacol. 1994 Sep;113(1):228–232. doi: 10.1111/j.1476-5381.1994.tb16198.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Karayalcin S. S., Sturbaum C. W., Wachsman J. T., Cha J. H., Powell D. W. Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport. J Clin Invest. 1990 Jul;86(1):60–68. doi: 10.1172/JCI114715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kostka P., Jang E., Watson E. G., Stewart J. L., Daniel E. E. Nitric oxide synthase in the autonomic nervous system of canine ileum. J Pharmacol Exp Ther. 1993 Jan;264(1):234–239. [PubMed] [Google Scholar]
  12. Llewellyn-Smith I. J., Song Z. M., Costa M., Bredt D. S., Snyder S. H. Ultrastructural localization of nitric oxide synthase immunoreactivity in guinea-pig enteric neurons. Brain Res. 1992 Apr 17;577(2):337–342. doi: 10.1016/0006-8993(92)90294-j. [DOI] [PubMed] [Google Scholar]
  13. MacNaughton W. K. Nitric oxide-donating compounds stimulate electrolyte transport in the guinea pig intestine in vitro. Life Sci. 1993;53(7):585–593. doi: 10.1016/0024-3205(93)90716-g. [DOI] [PubMed] [Google Scholar]
  14. Mascolo N., Izzo A. A., Barbato F., Capasso F. Inhibitors of nitric oxide synthetase prevent castor-oil-induced diarrhoea in the rat. Br J Pharmacol. 1993 Apr;108(4):861–864. doi: 10.1111/j.1476-5381.1993.tb13478.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miller M. J., Sadowska-Krowicka H., Chotinaruemol S., Kakkis J. L., Clark D. A. Amelioration of chronic ileitis by nitric oxide synthase inhibition. J Pharmacol Exp Ther. 1993 Jan;264(1):11–16. [PubMed] [Google Scholar]
  16. Moncada S., Higgs E. A. Endogenous nitric oxide: physiology, pathology and clinical relevance. Eur J Clin Invest. 1991 Aug;21(4):361–374. doi: 10.1111/j.1365-2362.1991.tb01383.x. [DOI] [PubMed] [Google Scholar]
  17. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  18. Nichols K., Staines W., Krantis A. Nitric oxide synthase distribution in the rat intestine: a histochemical analysis. Gastroenterology. 1993 Dec;105(6):1651–1661. doi: 10.1016/0016-5085(93)91060-u. [DOI] [PubMed] [Google Scholar]
  19. Nichols K., Staines W., Rubin S., Krantis A. Distribution of nitric oxide synthase activity in arterioles and venules of rat and human intestine. Am J Physiol. 1994 Aug;267(2 Pt 1):G270–G275. doi: 10.1152/ajpgi.1994.267.2.G270. [DOI] [PubMed] [Google Scholar]
  20. Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Robinson J. W., Antonioli J. A., Mirkovitch V. The intestinal response to ischaemia. Naunyn Schmiedebergs Arch Pharmakol Exp Pathol. 1966;255(2):178–191. doi: 10.1007/BF00543211. [DOI] [PubMed] [Google Scholar]
  22. Robinson J. W., Mirkovitch V. The recovery of function and microcirculation in small intestinal loops following ischaemia. Gut. 1972 Oct;13(10):784–789. doi: 10.1136/gut.13.10.784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Robinson J. W., Mirkovitch V., Winistörfer B., Saegesser F. Response of the intestinal mucosa to ischaemia. Gut. 1981 Jun;22(6):512–527. doi: 10.1136/gut.22.6.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Robinson J. W., Winistörfer B., Mirkovitch V. Source of net water and electrolyte loss following intestinal ischaemia. Res Exp Med (Berl) 1980;176(3):263–275. doi: 10.1007/BF01855846. [DOI] [PubMed] [Google Scholar]
  25. Rolfe V., Levin R. J. Enterotoxin Escherichia coli STa activates a nitric oxide-dependent myenteric plexus secretory reflex in the rat ileum. J Physiol. 1994 Mar 15;475(3):531–537. doi: 10.1113/jphysiol.1994.sp020091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rolston D. D., Borodo M. M., Kelly M. J., Dawson A. M., Farthing M. J. Efficacy of oral rehydration solutions in a rat model of secretory diarrhea. J Pediatr Gastroenterol Nutr. 1987 Jul-Aug;6(4):624–630. doi: 10.1097/00005176-198707000-00023. [DOI] [PubMed] [Google Scholar]
  27. Silk D. B., Fairclough P. D., Park N. J., Lane A. E., Webb J. P., Clark M. L., Dawson A. M. A study of relations between the absorption of amino acids, dipeptides, water and electrolytes in the normal human jejunum. Clin Sci Mol Med. 1975 Nov;49(5):401–408. doi: 10.1042/cs0490401. [DOI] [PubMed] [Google Scholar]
  28. Sladen G. E., Dawson A. M. Interrelationships between the absorptions of glucose, sodium and water by the normal human jejunum. Clin Sci. 1969 Feb;36(1):119–132. [PubMed] [Google Scholar]
  29. Stark M. E., Szurszewski J. H. Role of nitric oxide in gastrointestinal and hepatic function and disease. Gastroenterology. 1992 Dec;103(6):1928–1949. doi: 10.1016/0016-5085(92)91454-c. [DOI] [PubMed] [Google Scholar]
  30. Tamai H., Gaginella T. S. Direct evidence for nitric oxide stimulation of electrolyte secretion in the rat colon. Free Radic Res Commun. 1993;19(4):229–239. doi: 10.3109/10715769309056511. [DOI] [PubMed] [Google Scholar]
  31. Tepperman B. L., Brown J. F., Whittle B. J. Nitric oxide synthase induction and intestinal epithelial cell viability in rats. Am J Physiol. 1993 Aug;265(2 Pt 1):G214–G218. doi: 10.1152/ajpgi.1993.265.2.G214. [DOI] [PubMed] [Google Scholar]
  32. Tepperman B. L., Whittle B. J. Endogenous nitric oxide and sensory neuropeptides interact in the modulation of the rat gastric microcirculation. Br J Pharmacol. 1992 Jan;105(1):171–175. doi: 10.1111/j.1476-5381.1992.tb14230.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Whittle B. J., Lopez-Belmonte J., Moncada S. Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol. 1990 Mar;99(3):607–611. doi: 10.1111/j.1476-5381.1990.tb12977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wilson K. T., Xie Y., Musch M. W., Chang E. B. Sodium nitroprusside stimulates anion secretion and inhibits sodium chloride absorption in rat colon. J Pharmacol Exp Ther. 1993 Jul;266(1):224–230. [PubMed] [Google Scholar]

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