Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 May;103(1):1085–1091. doi: 10.1111/j.1476-5381.1991.tb12304.x

Bioassay of nitric oxide released upon stimulation of non-adrenergic non-cholinergic nerves in the canine ileocolonic junction.

G E Boeckxstaens 1, P A Pelckmans 1, I F Ruytjens 1, H Bult 1, J G De Man 1, A G Herman 1, Y M Van Maercke 1
PMCID: PMC1908082  PMID: 1908732

Abstract

1. The release and the nature of the inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitter was studied in the canine ileocolonic junction. A circular muscle strip of the canine ileocolonic junction served as donor tissue in a superfusion bioassay in which rings of rabbit aorta with the endothelium removed served as detector tissue. 2. The ileocolonic junction released a labile factor with vasodilator activity upon stimulation of non-adrenergic non-cholinergic (NANC) nerves in response to electrical impulses and the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP). This release was respectively frequency- and concentration-dependent. 3. The release was reduced by the blocker of neuronal conductance, tetrodotoxin, and by the inhibitor of the nitric oxide (NO) biosynthesis NG-nitro-L-arginine. The biological activity was enhanced by superoxide dismutase and eliminated by haemoglobin. Hexamethonium abolished only the release in response to DMPP. 4. Injection of adenosine 5'-triphosphate (ATP) or vasoactive intestinal polypeptide (VIP) onto the cascade induced relaxations of the rabbit aorta but they were different from those induced by NO or the transferable factor. 5. Based on organ bath experiments in which the reactivity of different parts of the circular smooth muscle layer of the ileocolonic junction was investigated, a muscle strip of superficial circular muscle with submucosa was chosen as the detector strip in the bioassay cascade. 6. The ileocolonic junction dose-dependently relaxed in response to nitroglycerin and NO. NO was much more potent in the rabbit aorta than in the canine ileocolonic junction.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1085

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., Bult H., De Man J. G., Herman A. G., Van Maercke Y. M. Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction. Eur J Pharmacol. 1990 Nov 6;190(1-2):239–246. doi: 10.1016/0014-2999(90)94132-h. [DOI] [PubMed] [Google Scholar]
  2. Boeckxstaens G. E., Pelckmans P. A., Bult H., De Man J. G., Herman A. G., van Maercke Y. M. Evidence for nitric oxide as mediator of non-adrenergic non-cholinergic relaxations induced by ATP and GABA in the canine gut. Br J Pharmacol. 1991 Feb;102(2):434–438. doi: 10.1111/j.1476-5381.1991.tb12191.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boeckxstaens G. E., Pelckmans P. A., Rampart M., Ruytjens I. F., Verbeuren T. J., Herman A. G., Van Maercke Y. M. GABAA receptor-mediated stimulation of non-adrenergic non-cholinergic neurones in the dog ileocolonic junction. Br J Pharmacol. 1990 Oct;101(2):460–464. doi: 10.1111/j.1476-5381.1990.tb12730.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
  5. Buga G. M., Gold M. E., Wood K. S., Chaudhuri G., Ignarro L. J. Endothelium-derived nitric oxide relaxes nonvascular smooth muscle. Eur J Pharmacol. 1989 Feb 14;161(1):61–72. doi: 10.1016/0014-2999(89)90180-5. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Bult H., Fret H. R., Van den Bossche R. M., Herman A. G. Platelet inhibition by endothelium-derived relaxing factor from the rabbit perfused aorta. Br J Pharmacol. 1988 Dec;95(4):1308–1314. doi: 10.1111/j.1476-5381.1988.tb11769.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Burnstock G., Costa M. Inhibitory innervation of the gut. Gastroenterology. 1973 Jan;64(1):141–144. [PubMed] [Google Scholar]
  9. Burnstock G. Purinergic nerves. Pharmacol Rev. 1972 Sep;24(3):509–581. [PubMed] [Google Scholar]
  10. 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]
  11. Burnstock G. The non-adrenergic non-cholinergic nervous system. Arch Int Pharmacodyn Ther. 1986 Apr;280(2 Suppl):1–15. [PubMed] [Google Scholar]
  12. Cocks T. M., Angus J. A. Comparison of relaxation responses of vascular and non-vascular smooth muscle to endothelium-derived relaxing factor (EDRF), acidified sodium nitrite (NO) and sodium nitroprusside. Naunyn Schmiedebergs Arch Pharmacol. 1990 Apr;341(4):364–372. doi: 10.1007/BF00180663. [DOI] [PubMed] [Google Scholar]
  13. Dickie B. G., Lewis M. J., Davies J. A. Potassium-stimulated release of nitric oxide from cerebellar slices. Br J Pharmacol. 1990 Sep;101(1):8–9. doi: 10.1111/j.1476-5381.1990.tb12078.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dusting G. J., Read M. A., Stewart A. G. Endothelium-derived relaxing factor released from cultured cells: differentiation from nitric oxide. Clin Exp Pharmacol Physiol. 1988 Feb;15(2):83–92. doi: 10.1111/j.1440-1681.1988.tb01049.x. [DOI] [PubMed] [Google Scholar]
  15. Furchgott R. F. The role of endothelium in the responses of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol. 1984;24:175–197. doi: 10.1146/annurev.pa.24.040184.001135. [DOI] [PubMed] [Google Scholar]
  16. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. Gillespie J. S., Sheng H. Influence of haemoglobin and erythrocytes on the effects of EDRF, a smooth muscle inhibitory factor, and nitric oxide on vascular and non-vascular smooth muscle. Br J Pharmacol. 1988 Dec;95(4):1151–1156. doi: 10.1111/j.1476-5381.1988.tb11750.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Griffith T. M., Edwards D. H., Lewis M. J., Newby A. C., Henderson A. H. The nature of endothelium-derived vascular relaxant factor. Nature. 1984 Apr 12;308(5960):645–647. doi: 10.1038/308645a0. [DOI] [PubMed] [Google Scholar]
  23. Gryglewski R. J., Palmer R. M., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986 Apr 3;320(6061):454–456. doi: 10.1038/320454a0. [DOI] [PubMed] [Google Scholar]
  24. Herman A. G., Bogaert M. G., De Schaepdryver A. F. Effect of nitroglycerin at different degrees of contraction of the rabbit aortic strip. Arch Int Pharmacodyn Ther. 1971 Apr;190(2):407–408. [PubMed] [Google Scholar]
  25. Ignarro L. J. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol. 1990;30:535–560. doi: 10.1146/annurev.pa.30.040190.002535. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  29. 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]
  30. Myers P. R., Minor R. L., Jr, Guerra R., Jr, Bates J. N., Harrison D. G. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature. 1990 May 10;345(6271):161–163. doi: 10.1038/345161a0. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. Palmer R. M., Rees D. D., Ashton D. S., Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251–1256. doi: 10.1016/s0006-291x(88)81362-7. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. 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]
  37. 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]
  38. Shikano K., Ohlstein E. H., Berkowitz B. A. Differential selectivity of endothelium-derived relaxing factor and nitric oxide in smooth muscle. Br J Pharmacol. 1987 Nov;92(3):483–485. doi: 10.1111/j.1476-5381.1987.tb11347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Smith T. K., Reed J. B., Sanders K. M. Electrical pacemakers of canine proximal colon are functionally innervated by inhibitory motor neurons. Am J Physiol. 1989 Mar;256(3 Pt 1):C466–C477. doi: 10.1152/ajpcell.1989.256.3.C466. [DOI] [PubMed] [Google Scholar]
  40. Smith T. K., Reed J. B., Sanders K. M. Interaction of two electrical pacemakers in muscularis of canine proximal colon. Am J Physiol. 1987 Mar;252(3 Pt 1):C290–C299. doi: 10.1152/ajpcell.1987.252.3.C290. [DOI] [PubMed] [Google Scholar]
  41. Smith T. K., Reed J. B., Sanders K. M. Origin and propagation of electrical slow waves in circular muscle of canine proximal colon. Am J Physiol. 1987 Feb;252(2 Pt 1):C215–C224. doi: 10.1152/ajpcell.1987.252.2.C215. [DOI] [PubMed] [Google Scholar]
  42. Tucker J. F., Brave S. R., Charalambous L., Hobbs A. J., Gibson A. L-NG-nitro arginine inhibits non-adrenergic, non-cholinergic relaxations of guinea-pig isolated tracheal smooth muscle. Br J Pharmacol. 1990 Aug;100(4):663–664. doi: 10.1111/j.1476-5381.1990.tb14072.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Waldman S. A., Murad F. Cyclic GMP synthesis and function. Pharmacol Rev. 1987 Sep;39(3):163–196. [PubMed] [Google Scholar]

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

RESOURCES