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. 1991 Feb;102(2):434–438. doi: 10.1111/j.1476-5381.1991.tb12191.x

Evidence for nitric oxide as mediator of non-adrenergic non-cholinergic relaxations induced by ATP and GABA in the canine gut.

G E Boeckxstaens 1, P A Pelckmans 1, H Bult 1, J G De Man 1, A G Herman 1, Y M van Maercke 1
PMCID: PMC1918030  PMID: 1673072

Abstract

1 The effects of haemoglobin, and the nitric oxide (NO) biosynthesis-inhibitors NG-monomethyl-L-arginine (L-NMMA), its enantiomer D-NMMA, and NG-nitro-L-arginine (L-NNA) were investigated on nonadrenergic non-cholinergic (NANC)-mediated relaxation of circular muscle strips of the canine terminal ileum and ileocolonic junction induced by electrical stimulation, adenosine 5'-triphosphate (ATP), gamma-aminobutyric acid (GABA) and NO. 2 Tetrodotoxin, L-NMMA and L-NNA, but not D-NMMA, inhibited the relaxations induced by electrical stimulation, ATP and GABA, but not those in response to NO. 3 The inhibitory effect of L-NMMA and L-NNA was prevented by L-arginine, but not by D-arginine. L-Arginine did not potentiate any of the NANC relaxations. 4 Haemoglobin reduced the relaxation induced by electrical stimulation, ATP and GABA, and abolished those in response to NO. 5 Our results demonstrate that the ATP- and GABA-induced relaxations resulting from stimulation of intramural NANC neurones, in addition to those induced by electrical impulses, are mediated by NO or a NO releasing substance and thus provide further evidence in support of the proposal that NO is the final inhibitory NANC neurotransmitter in the canine terminal ileum and ileocolonic junction.

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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., Rampart M., Bogers J. J., Verbeuren T. J., Herman A. G., Van Maercke Y. M. Pharmacological characterization of 5-hydroxytryptamine receptors in the canine terminal ileum and ileocolonic junction. J Pharmacol Exp Ther. 1990 Aug;254(2):652–658. [PubMed] [Google Scholar]
  2. Bult H., Boeckxstaens G. E., Pelckmans P. A., Jordaens F. H., Van Maercke Y. M., Herman A. G. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature. 1990 May 24;345(6273):346–347. doi: 10.1038/345346a0. [DOI] [PubMed] [Google Scholar]
  3. Burnstock G., Costa M. Inhibitory innervation of the gut. Gastroenterology. 1973 Jan;64(1):141–144. [PubMed] [Google Scholar]
  4. Burnstock G. Purinergic nerves. Pharmacol Rev. 1972 Sep;24(3):509–581. [PubMed] [Google Scholar]
  5. Burnstock G. Review lecture. Neurotransmitters and trophic factors in the autonomic nervous system. J Physiol. 1981;313:1–35. doi: 10.1113/jphysiol.1981.sp013648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Garthwaite J., Charles S. L., Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988 Nov 24;336(6197):385–388. doi: 10.1038/336385a0. [DOI] [PubMed] [Google Scholar]
  7. Gibson A., Mirzazadeh S., Hobbs A. J., Moore P. K. L-NG-monomethyl arginine and L-NG-nitro arginine inhibit non-adrenergic, non-cholinergic relaxation of the mouse anococcygeus muscle. Br J Pharmacol. 1990 Mar;99(3):602–606. doi: 10.1111/j.1476-5381.1990.tb12976.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gillespie J. S., Liu X. R., Martin W. The effects of L-arginine and NG-monomethyl L-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation. Br J Pharmacol. 1989 Dec;98(4):1080–1082. doi: 10.1111/j.1476-5381.1989.tb12650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gillespie J. S., Sheng H. The effects of pyrogallol and hydroquinone on the response to NANC nerve stimulation in the rat anococcygeus and the bovine retractor penis muscles. Br J Pharmacol. 1990 Jan;99(1):194–196. doi: 10.1111/j.1476-5381.1990.tb14677.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goyal R. K., Rattan S., Said S. I. VIP as a possible neurotransmitter of non-cholinergic non-adrenergic inhibitory neurones. Nature. 1980 Nov 27;288(5789):378–380. doi: 10.1038/288378a0. [DOI] [PubMed] [Google Scholar]
  11. Grider J. R., Cable M. B., Said S. I., Makhlouf G. M. Vasoactive intestinal peptide as a neural mediator of gastric relaxation. Am J Physiol. 1985 Jan;248(1 Pt 1):G73–G78. doi: 10.1152/ajpgi.1985.248.1.G73. [DOI] [PubMed] [Google Scholar]
  12. Ignarro L. J., Buga G. M., Wood K. S., Byrns R. E., Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9265–9269. doi: 10.1073/pnas.84.24.9265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ishii K., Chang B., Kerwin J. F., Jr, Huang Z. J., Murad F. N omega-nitro-L-arginine: a potent inhibitor of endothelium-derived relaxing factor formation. Eur J Pharmacol. 1990 Feb 6;176(2):219–223. doi: 10.1016/0014-2999(90)90531-a. [DOI] [PubMed] [Google Scholar]
  14. Kelm M., Feelisch M., Spahr R., Piper H. M., Noack E., Schrader J. Quantitative and kinetic characterization of nitric oxide and EDRF released from cultured endothelial cells. Biochem Biophys Res Commun. 1988 Jul 15;154(1):236–244. doi: 10.1016/0006-291x(88)90675-4. [DOI] [PubMed] [Google Scholar]
  15. Knowles R. G., Palacios M., Palmer R. M., Moncada S. Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5159–5162. doi: 10.1073/pnas.86.13.5159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maggi C. A., Manzini S., Meli A. Evidence that GABAA receptors mediate relaxation of rat duodenum by activating intramural nonadrenergic-noncholinergic neurones. J Auton Pharmacol. 1984 Jun;4(2):77–85. doi: 10.1111/j.1474-8673.1984.tb00084.x. [DOI] [PubMed] [Google Scholar]
  17. Manzini S., Maggi C. A., Meli A. Further evidence for involvement of adenosine-5'-triphosphate in non-adrenergic non-cholinergic relaxation of the isolated rat duodenum. Eur J Pharmacol. 1985 Jul 31;113(3):399–408. doi: 10.1016/0014-2999(85)90088-3. [DOI] [PubMed] [Google Scholar]
  18. Moncada S., Palmer R. M., Higgs E. A. Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989 Jun 1;38(11):1709–1715. doi: 10.1016/0006-2952(89)90403-6. [DOI] [PubMed] [Google Scholar]
  19. Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mülsch A., Busse R. NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):143–147. doi: 10.1007/BF00195071. [DOI] [PubMed] [Google Scholar]
  21. Palmer R. M., Ashton D. S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. doi: 10.1038/333664a0. [DOI] [PubMed] [Google Scholar]
  22. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  23. Pelckmans P. A., Boeckxstaens G. E., Van Maercke Y. M., Herman A. G., Verbeuren T. J. Acetylcholine is an indirect inhibitory transmitter in the canine ileocolonic junction. Eur J Pharmacol. 1989 Nov 7;170(3):235–242. doi: 10.1016/0014-2999(89)90544-x. [DOI] [PubMed] [Google Scholar]
  24. Pelckmans P. A., Van Maercke Y. M., De Maeyer M. H., Herman A. G., Verbeuren T. J. Cholinergic and adrenergic contractile properties of the canine ileocolonic junction. J Pharmacol Exp Ther. 1990 Jul;254(1):158–164. [PubMed] [Google Scholar]
  25. Ramagopal M. V., Leighton H. J. Effects of NG-monomethyl-L-arginine on field stimulation-induced decreases in cytosolic Ca2+ levels and relaxation in the rat anococcygeus muscle. Eur J Pharmacol. 1989 Dec 19;174(2-3):297–299. doi: 10.1016/0014-2999(89)90325-7. [DOI] [PubMed] [Google Scholar]
  26. Schmidt H. H., Nau H., Wittfoht W., Gerlach J., Prescher K. E., Klein M. M., Niroomand F., Böhme E. Arginine is a physiological precursor of endothelium-derived nitric oxide. Eur J Pharmacol. 1988 Sep 13;154(2):213–216. doi: 10.1016/0014-2999(88)90101-x. [DOI] [PubMed] [Google Scholar]

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