Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Sep;113(1):228–232. doi: 10.1111/j.1476-5381.1994.tb16198.x

Nitric oxide as a mediator of the laxative action of magnesium sulphate.

A A Izzo 1, T S Gaginella 1, N Mascolo 1, F Capasso 1
PMCID: PMC1510055  PMID: 7529110

Abstract

1. Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion, gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2. At a dose of 2 g kg-1 orally magnesium sulphate produced diarrhoea that was delayed in onset and intensity in a dose-related manner by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L-arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3. Nitric oxide synthase activity was stimulated in gut tissue from rats given magnesium sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-1, i.p.), an inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced diarrhoea. 4. Magnesium sulphate stimulated fluid and electrolyte accumulation in the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5. Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P < 0.01), and this was prevented by pretreatment with L-NAME. 6. The results demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing the accumulation of fluid in the intestinal lumen and enhancing flow from the proximal to distal intestine. The mechanism involves release of NO, probably through stimulation of the constitutive form of NO synthase. Whether or not the effects of magnesium sulphate are due to an osmotic action or an intrinsic effect of the magnesium or sulphate ions cannot be determined from these experiments.

Full text

PDF
228

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boeckxstaens G. E., Pelckmans P. A., Herman A. G., Van Maercke Y. M. Involvement of nitric oxide in the inhibitory innervation of the human isolated colon. Gastroenterology. 1993 Mar;104(3):690–697. doi: 10.1016/0016-5085(93)91003-z. [DOI] [PubMed] [Google Scholar]
  2. Boyde T. R., Rahmatullah M. Optimization of conditions for the colorimetric determination of citrulline, using diacetyl monoxime. Anal Biochem. 1980 Sep 15;107(2):424–431. doi: 10.1016/0003-2697(80)90404-2. [DOI] [PubMed] [Google Scholar]
  3. Bussjaeger L. J., Johnson L. R. Evidence for hormonal regulation of intestinal absorption by cholecystokinin. Am J Physiol. 1973 Jun;224(6):1276–1279. doi: 10.1152/ajplegacy.1973.224.6.1276. [DOI] [PubMed] [Google Scholar]
  4. Calignano A., Moncada S., Di Rosa M. Endogenous nitric oxide modulates morphine-induced constipation. Biochem Biophys Res Commun. 1991 Dec 16;181(2):889–893. doi: 10.1016/0006-291x(91)91274-g. [DOI] [PubMed] [Google Scholar]
  5. Grider J. R. Interplay of VIP and nitric oxide in regulation of the descending relaxation phase of peristalsis. Am J Physiol. 1993 Feb;264(2 Pt 1):G334–G340. doi: 10.1152/ajpgi.1993.264.2.G334. [DOI] [PubMed] [Google Scholar]
  6. Harvey R. F., Read A. E. Saline purgatives act by releasing cholecystokinin. Lancet. 1973 Jul;2(7822):185–187. doi: 10.1016/s0140-6736(73)93011-0. [DOI] [PubMed] [Google Scholar]
  7. Hubel K. A. Effects of pentagastrin and cholecystikinin on intestinal transport of ions and water in the rat. Proc Soc Exp Biol Med. 1972 Jun;140(2):670–672. doi: 10.3181/00379727-140-36527. [DOI] [PubMed] [Google Scholar]
  8. Kachur J. F., Phillips G. S., Gaginella T. S. Neuromodulation of guinea pig intestinal electrolyte transport by cholecystokinin octapeptide. Gastroenterology. 1991 Feb;100(2):344–349. doi: 10.1016/0016-5085(91)90201-u. [DOI] [PubMed] [Google Scholar]
  9. Malagelada J. R., Holtermuller K. H., McCall J. T., Go V. L. Pancreatic, gallbladder, and intestinal responses to intraluminal magnesium salts in man. Am J Dig Dis. 1978 Jun;23(6):481–485. doi: 10.1007/BF01072690. [DOI] [PubMed] [Google Scholar]
  10. Mascolo N., Izzo A. A., Autore G., Barbato F., Capasso F. Nitric oxide and castor oil-induced diarrhea. J Pharmacol Exp Ther. 1994 Jan;268(1):291–295. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Moritz M., Finkelstein G., Meshkinpour H., Fingerut J., Lorber S. H. Effect of secretin and cholecystokinin on the transport of electrolyte and water in human jejunum. Gastroenterology. 1973 Jan;64(1):76–80. [PubMed] [Google Scholar]
  14. Murthy K. S., Zhang K. M., Jin J. G., Grider J. R., Makhlouf G. M. VIP-mediated G protein-coupled Ca2+ influx activates a constitutive NOS in dispersed gastric muscle cells. Am J Physiol. 1993 Oct;265(4 Pt 1):G660–G671. doi: 10.1152/ajpgi.1993.265.4.G660. [DOI] [PubMed] [Google Scholar]
  15. Stark M. E., Bauer A. J., Sarr M. G., Szurszewski J. H. Nitric oxide mediates inhibitory nerve input in human and canine jejunum. Gastroenterology. 1993 Feb;104(2):398–409. doi: 10.1016/0016-5085(93)90407-4. [DOI] [PubMed] [Google Scholar]
  16. Stewart J. J., Gaginella T. S., Olsen W. A., Bass P. Inhibitory actions of laxatives on motility and water and electrolyte transport in the gastrointestinal tract. J Pharmacol Exp Ther. 1975 Feb;192(2):458–467. [PubMed] [Google Scholar]
  17. 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]
  18. Van Hoestenberghe A., De Witte P., Geboes K., Eyssen H., Nijs G., Lemli J. The effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free rats. Eur J Pharmacol. 1992 Feb 25;212(1):121–123. doi: 10.1016/0014-2999(92)90084-h. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES