Digestive Diseases and Sciences

, Volume 39, Issue 9, pp 1872–1876 | Cite as

Nerve-mediated nitric oxide production by opossum lower esophageal sphincter

  • J. Murray
  • J. N. Bates
  • J. L. Conklin
Esophageal, Gastric, And Duodenal Disorders


Antagonists of nitric oxide synthesis inhibit nerve-induced hyperpolarization and relaxation of muscle from the opossum lower esophageal sphincter. These studies test the hypothesis that nitric oxide is released during stimulation of intrinsic esophageal nerves. The intrinsic nerves were stimulated with an electrical field (10-sec trains of 1-msec, 30-V pulses delivered at 10 Hz). Nitric oxide production was measured with a DASIBI model 2108 Chemiluminescence NO Analyzer.NG-Nitro-l-arginine, an inhibitor of NO synthase, antagonized nerve-induced relaxation the lower esophageal sphincter. Nerve stimulation increased NO production from 0.50±0.04 nmol/min/100 mg tissue to 0.87±0.07 nmol/min/100 mg tissue (P<0.01).NG-nitro-l-arginine inhibited both basal (0.030±0.09 nmol/min/100 mg tissue,P<0.05 vs baseline) and stimulated (0.38±0.10 nmol/min/100 mg tissue,P<0.01 vs stimulated). These studies support the hypothesis that nerve stimulation releases nitric oxide from the lower esophageal sphincter.

Key words

enteric nervous system nonadrenergic noncholinergic nerves esophagus gastrointestinal motility peristalsis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Boeckxstaens GE, Pelkmans PA, Bogers JJ, Bult H, De Man JG, Oosterbosch L, Herman G, Van Maercke YM: Release of nitric oxide upon stimulation of nonadrenergic noncholinergic nerves of the guinea pig fundus. J Pharmacol Exp Ther 256:441–447, 1990Google Scholar
  2. 2.
    Boeckxstaens GE, Pelkmans PA, Bult H, De Man JG, Herman G, Van Maercke YM: Nonadrenergic noncholinergic relaxation mediated by nitric oxide in the ileocolonic junction. Br J Pharmacol 101:460–464, 1990PubMedGoogle Scholar
  3. 3.
    Dalziel HH, Thornbury KD, Ward SM, Sanders KM: Involvement of nitric oxide synthetic pathway in inhibitory junction potentials in canine proximal colon. Am J Physiol 260:G789-G792, 1991PubMedGoogle Scholar
  4. 4.
    Desai KM, Sessa WC, Vane JR: Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food and fluid. Nature 351:477–479, 1991PubMedGoogle Scholar
  5. 5.
    Du C, Murray J, Conklin JL: Cyclic GMP mediates nitric oxide-produced NANC hyperpolarization of opossum esophageal circular smooth muscle. Gastroenterology 102:A443, 1992Google Scholar
  6. 6.
    Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM: Nitric oxide: A cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157:87–94, 1988PubMedGoogle Scholar
  7. 7.
    Sanders K, Ward SM: Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol 262:G379-G392, 1992PubMedGoogle Scholar
  8. 8.
    Stark ME, Bauer AJ, Szurszewski JH: Effect of nitric oxide on circular muscle of the canine small intestine. J Physiol London 444:743–761, 1991PubMedGoogle Scholar
  9. 9.
    Toda N, Baba H, Okamura T: Role of nitric oxide in nonadrenergic, noncholinergic nerve-mediated relaxation in dog duodenal longitudinal muscle strips. Jpn J Pharmacol 53:281–284, 1990PubMedGoogle Scholar
  10. 10.
    Ward SM, Dalziel HH, Thornbury KD, Westfall D, Sanders KM: Nonadrenergic, noncholinergic inhibition and excitation in canine colon depend on nitric oxide. Am J Physiol 262:G237-G243, 1992PubMedGoogle Scholar
  11. 11.
    Conklin JL, Du C, Murray JA, Bates JN: Characterization and mediator of inhibitory junction potentials of opossum lower esophageal sphincter. Gastroenterology (submitted)Google Scholar
  12. 12.
    Du C, Murray J, Bates J, Conklin JL: Nitric oxide: Mediator of nonadrenergic noncholinergic hyperpolarization of opossum esophageal muscle. Am J Physiol 261:G1012-G1016, 1991PubMedGoogle Scholar
  13. 13.
    Murray J, Du C, Ledlow A, Bates JN, Conklin JL: Nitric oxide: Mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle. Am J Physiol 261:G401-G406, 1991PubMedGoogle Scholar
  14. 14.
    Tottrup A, Svane D, Forman A: Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol 260:G385-G389, 1991PubMedGoogle Scholar
  15. 15.
    Yamato S, Spechler SJ, Goyal RK: Role of nitric oxide in esophageal peristalsis in the opossum. Gastroenterology 103:197–204, 1992PubMedGoogle Scholar
  16. 16.
    Fang S, Christensen J: Distribution of NADPH diaphorase in intramural plexuses of cat and opossum esophagus. J Auton Nerv Syst 46:123–133, 1993Google Scholar
  17. 17.
    Cox RD: Determination of nitrate and nitrite at the parts per billion level by chemiluminescence. Anal Chem 52:332–335, 1980Google Scholar
  18. 18.
    Myers PR, Minor RL, Guerra R Jr, Bates JN, Harrison DG: Vasorelaxant properties of the endothelium-derived relaxing factor more closely resembleS-nitrosocysteine than nitric oxide. Nature 345:161–163, 1990PubMedGoogle Scholar
  19. 19.
    Christensen J, Conklin JL, Freeman BF: Physiologic specialization at espohagogastric junction in three species. Am J Physiol 225:1265–1270, 1973PubMedGoogle Scholar
  20. 20.
    Moore PK, Al-Swayeh OA, Chong NSW, Evans RA, Gibson A:l-N G-nitro-arginine (l-NOARG), a novel,l-arginine-reversible inhibitor of endothelium-dependent vasodilatationin vitro. Br J Pharmacol 99:408–412, 1990PubMedGoogle Scholar
  21. 21.
    Mulsch A, Busse R:N G-nitro-l-arginine (N5-[imino(nitroamino-methyl]-l-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis froml-arginine. Naunyn-Schmiedeberg's Arch Pharmacol 341:143–147, 1990Google Scholar
  22. 22.
    Salvemini D, DeNucci D, Gryglewski RJ, Vane RJ: Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing nitric oxide. Proc Natl Acad Sci USA 86:6328–6332, 1989PubMedGoogle Scholar
  23. 23.
    Salvemini D, Masini E, Anggard E, Mannaioni PF, Vane JR: Synthesis of a nitric oxide-like factor from L-arginine by rat serosal mast cells: Stimulation of guanylate cyclase and inhibition of platelet aggregation. Biochem Biophys Res Commun 169:596–601, 1990PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • J. Murray
    • 1
  • J. N. Bates
    • 1
  • J. L. Conklin
    • 1
  1. 1.From the Departments of Internal Medicine and AnesthesiologyUniversity of Iowa College of Medicine and Department of Veterans Affairs Medical CenterIowa City

Personalised recommendations