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. 1994 Dec;35(12):1690–1696. doi: 10.1136/gut.35.12.1690

Nitrinergic and peptidergic innervation of the human oesophagus.

C Singaram 1, A Sengupta 1, M A Sweet 1, D J Sugarbaker 1, R K Goyal 1
PMCID: PMC1375254  PMID: 7530228

Abstract

The distribution, colocalisation, and interconnections of nitrinergic and peptidergic neurons and nerves in the human oesophagus were examined. Cryosections of surgically resected tissues from eight subjects were studied with indirect immunofluorescence for the presence of 11 neuropeptides and neuron specific enolase. After immunohistochemistry, nitric oxide synthase was shown on the same sections with the beta nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical reaction. The histochemical findings were verified immunohistochemically on other sections with an antiserum against nitric oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%) received terminations positive for vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase containing fibers seen in the muscle layers, many had closely associated VIP and galanin, but only rarely CGRP and substance P. Thus, despite abundant representation of both peptidergic and nitrinergic systems in oesophageal smooth muscle, only VIP and galanin colocalised to any significant extent with the nitrinergic elements. These findings provide morphological support for the role of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the human oesophagus and for its possible interactive role with the peptidergic system.

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Selected References

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  1. Abdelrahman A., Wang Y. X., Chang S. D., Pang C. C. Mechanism of the vasodilator action of calcitonin gene-related peptide in conscious rats. Br J Pharmacol. 1992 May;106(1):45–48. doi: 10.1111/j.1476-5381.1992.tb14290.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aggestrup S. Effect of regulatory polypeptides on the substance P stimulated lower esophageal sphincter pressure in pigs. Regul Pept. 1985 Sep;12(1):1–7. doi: 10.1016/0167-0115(85)90181-8. [DOI] [PubMed] [Google Scholar]
  3. Aggestrup S., Uddman R., Jensen S. L., Håkanson R., Sundler F., Schaffalitzky de Muckadell O., Emson P. Regulatory peptides in lower esophageal sphincter of pig and man. Dig Dis Sci. 1986 Dec;31(12):1370–1375. doi: 10.1007/BF01299816. [DOI] [PubMed] [Google Scholar]
  4. Allescher H. D., Tougas G., Vergara P., Lu S., Daniel E. E. Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo. Am J Physiol. 1992 Apr;262(4 Pt 1):G695–G702. doi: 10.1152/ajpgi.1992.262.4.G695. [DOI] [PubMed] [Google Scholar]
  5. Bredt D. S., Glatt C. E., Hwang P. M., Fotuhi M., Dawson T. M., Snyder S. H. Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron. 1991 Oct;7(4):615–624. doi: 10.1016/0896-6273(91)90374-9. [DOI] [PubMed] [Google Scholar]
  6. Christensen J., Williams T. H., Jew J., O'Dorisio T. M. Distribution of vasoactive intestinal polypeptide-immunoreactive structures in the opossum esophagus. Gastroenterology. 1987 Apr;92(4):1007–1018. doi: 10.1016/0016-5085(87)90977-2. [DOI] [PubMed] [Google Scholar]
  7. Daniel E. E., Jager L. P., Jury J. Vasoactive intestinal polypeptide and non-adrenergic, non-cholinergic inhibition in lower oesophageal sphincter of opossum. Br J Pharmacol. 1989 Mar;96(3):746–752. doi: 10.1111/j.1476-5381.1989.tb11877.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dawson T. M., Bredt D. S., Fotuhi M., Hwang P. M., Snyder S. H. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7797–7801. doi: 10.1073/pnas.88.17.7797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Du C., Murray J., Bates J. N., Conklin J. L. Nitric oxide: mediator of NANC hyperpolarization of opossum esophageal smooth muscle. Am J Physiol. 1991 Dec;261(6 Pt 1):G1012–G1016. doi: 10.1152/ajpgi.1991.261.6.G1012. [DOI] [PubMed] [Google Scholar]
  10. Gabella G. Detection of nerve cells by a histochemical technic. Experientia. 1969 Feb 15;25(2):218–219. doi: 10.1007/BF01899135. [DOI] [PubMed] [Google Scholar]
  11. Gray D. W., Marshall I. Nitric oxide synthesis inhibitors attenuate calcitonin gene-related peptide endothelium-dependent vasorelaxation in rat aorta. Eur J Pharmacol. 1992 Feb 25;212(1):37–42. doi: 10.1016/0014-2999(92)90069-g. [DOI] [PubMed] [Google Scholar]
  12. Grider J. R., Murthy K. S., Jin J. G., Makhlouf G. M. Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release. Am J Physiol. 1992 Apr;262(4 Pt 1):G774–G778. doi: 10.1152/ajpgi.1992.262.4.G774. [DOI] [PubMed] [Google Scholar]
  13. Hope B. T., Michael G. J., Knigge K. M., Vincent S. R. Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2811–2814. doi: 10.1073/pnas.88.7.2811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knudsen M. A., Svane D., Tøttrup A. Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter. Am J Physiol. 1992 May;262(5 Pt 1):G840–G846. doi: 10.1152/ajpgi.1992.262.5.G840. [DOI] [PubMed] [Google Scholar]
  15. Leander S., Brodin E., Håkanson R., Sundler F., Uddman R. Neuronal substance P in the esophagus. Distribution and effects on motor activity. Acta Physiol Scand. 1982 Aug;115(4):427–435. doi: 10.1111/j.1748-1716.1982.tb07101.x. [DOI] [PubMed] [Google Scholar]
  16. Murray J., Du C., Ledlow A., Bates J. N., Conklin J. L. Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle. Am J Physiol. 1991 Sep;261(3 Pt 1):G401–G406. doi: 10.1152/ajpgi.1991.261.3.G401. [DOI] [PubMed] [Google Scholar]
  17. Osthaus L. E., Galligan J. J. Antagonists of nitric oxide synthesis inhibit nerve-mediated relaxations of longitudinal muscle in guinea pig ileum. J Pharmacol Exp Ther. 1992 Jan;260(1):140–145. [PubMed] [Google Scholar]
  18. Rattan S., Gonnella P., Goyal R. K. Inhibitory effect of calcitonin gene-related peptide and calcitonin on opossum esophageal smooth muscle. Gastroenterology. 1988 Feb;94(2):284–293. doi: 10.1016/0016-5085(88)90414-3. [DOI] [PubMed] [Google Scholar]
  19. Rodrigo J., Polak J. M., Fernandez L., Ghatei M. A., Mulderry P., Bloom S. R. Calcitonin gene-related peptide immunoreactive sensory and motor nerves of the rat, cat, and monkey esophagus. Gastroenterology. 1985 Feb;88(2):444–451. doi: 10.1016/0016-5085(85)90505-0. [DOI] [PubMed] [Google Scholar]
  20. Sanders K. M., Ward S. M. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol. 1992 Mar;262(3 Pt 1):G379–G392. doi: 10.1152/ajpgi.1992.262.3.G379. [DOI] [PubMed] [Google Scholar]
  21. Singaram C., Sengupta A., Spechler S. J., Goyal R. K. Mucosal peptidergic innervation of the opossum esophagus and anal canal: a comparison with snout skin. J Auton Nerv Syst. 1990 Mar;29(3):231–240. doi: 10.1016/0165-1838(90)90149-d. [DOI] [PubMed] [Google Scholar]
  22. Singaram C., Sengupta A., Sugarbaker D. J., Goyal R. K. Peptidergic innervation of the human esophageal smooth muscle. Gastroenterology. 1991 Nov;101(5):1256–1263. doi: 10.1016/0016-5085(91)90075-v. [DOI] [PubMed] [Google Scholar]
  23. Snyder S. H. Nitric oxide: first in a new class of neurotransmitters. Science. 1992 Jul 24;257(5069):494–496. doi: 10.1126/science.1353273. [DOI] [PubMed] [Google Scholar]
  24. Sundler F., Håkanson R., Leander S. Peptidergic nervous systems in the gut. Clin Gastroenterol. 1980 Sep;9(3):517–543. [PubMed] [Google Scholar]
  25. Tam P. K., Lister J. Development profile of neuron-specific enolase in human gut and its implications in Hirschsprung's disease. Gastroenterology. 1986 Jun;90(6):1901–1906. doi: 10.1016/0016-5085(86)90259-3. [DOI] [PubMed] [Google Scholar]
  26. Tøttrup A., Forman A., Funch-Jensen P., Raundahl U., Andersson K. E. Effects of transmural field stimulation in isolated muscle strips from human esophagus. Am J Physiol. 1990 Mar;258(3 Pt 1):G344–G351. doi: 10.1152/ajpgi.1990.258.3.G344. [DOI] [PubMed] [Google Scholar]
  27. Tøttrup A., Svane D., Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol. 1991 Mar;260(3 Pt 1):G385–G389. doi: 10.1152/ajpgi.1991.260.3.G385. [DOI] [PubMed] [Google Scholar]
  28. Uddman R., Alumets J., Edvinsson L., Håkanson R., Sundler F. Peptidergic (VIP) innervation of the esophagus. Gastroenterology. 1978 Jul;75(1):5–8. [PubMed] [Google Scholar]
  29. Wattchow D. A., Furness J. B., Costa M., O'Brien P. E., Peacock M. Distributions of neuropeptides in the human esophagus. Gastroenterology. 1987 Dec;93(6):1363–1371. doi: 10.1016/0016-5085(87)90267-8. [DOI] [PubMed] [Google Scholar]
  30. Yamato S., Saha J. K., Goyal R. K. Role of nitric oxide in lower esophageal sphincter relaxation to swallowing. Life Sci. 1992;50(17):1263–1272. doi: 10.1016/0024-3205(92)90326-k. [DOI] [PubMed] [Google Scholar]
  31. Yamato S., Spechler S. J., Goyal R. K. Role of nitric oxide in esophageal peristalsis in the opossum. Gastroenterology. 1992 Jul;103(1):197–204. doi: 10.1016/0016-5085(92)91113-i. [DOI] [PubMed] [Google Scholar]
  32. Young H. M., Furness J. B., Shuttleworth C. W., Bredt D. S., Snyder S. H. Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea-pig intestine. Histochemistry. 1992 May;97(4):375–378. doi: 10.1007/BF00270041. [DOI] [PubMed] [Google Scholar]

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