{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:00:00Z","timestamp":1783472400249,"version":"3.55.0"},"reference-count":33,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1994,12]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1136\/gut.35.12.1690","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"1690-1696","source":"Crossref","is-referenced-by-count":73,"title":["Nitrinergic and peptidergic innervation of the human oesophagus."],"prefix":"10.1136","volume":"35","author":[{"given":"C","family":"Singaram","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Sengupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Sweet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"Sugarbaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R K","family":"Goyal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1994,12,1]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Histochemistry of the enteric nervous system","volume-title":"Physiology of the gastrointestinal tract. Vol 1","author":"Costa, M.; Furness, J.B.; Llewellyn-Smith, I.F.","year":"1987","unstructured":"Costa M, Furness JB, Llewellyn-Smith IF. Histochemistry of the enteric nervous system. In: Johnson LR, ed. Physiology of the gastrointestinal tract. Vol 1. 2nd ed. New York: Raven, 1987: 1-40.","edition":"2nd ed"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/0016-5085(88)90414-3","article-title":"Inhibitory effect of calcitonin gene-related peptide and calcitonin on opossum esophageal smooth muscle","volume":"94","author":"Rattan, S.; Gonnella, P.; Goyal, R.K.","year":"1988","unstructured":"Rattan S, Gonnella P, Goyal RK. Inhibitory effect of calcitonin gene-related peptide and calcitonin on opossum esophageal smooth muscle. Gastroenterology 1988; 94: 284-93.","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1111\/j.1476-5381.1989.tb11877.x","article-title":"Vasoactive intestinal polypeptide and non-adrenergic, non-cholinergic inhibition in lower oesophageal sphincter of opossum","volume":"96","author":"Daniel, E.E.; Jager, L.P.; Jury, J.","year":"1989","unstructured":"Daniel EE, Jager LP, Jury J. Vasoactive intestinal polypeptide and non-adrenergic, non-cholinergic inhibition in lower oesophageal sphincter of opossum. Br Jf Pharmacol 1989; 96: 746-52.","journal-title":"Br Jf Pharmacol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0167-0115(85)90181-8","article-title":"Effect of regulatory polypeptide on the substance P stimulated lower oesophageal sphincter pressure in pigs","volume":"12","author":"Aggestrup, S.","year":"1985","unstructured":"Aggestrup S. Effect of regulatory polypeptide on the substance P stimulated lower oesophageal sphincter pressure in pigs. Regul Pept 1985; 12: 1-7.","journal-title":"Regul Pept"},{"key":"ref_5","first-page":"5","volume-title":"Peptidergic (VIP) innervation of the esophagus. Gastroenterology 1978; 75","author":"Uddman, R.; Alumets, J.; Edvinsson, L.; Hakanson, R.; Sundler, F.","unstructured":"Uddman R, Alumets J, Edvinsson L, Hakanson R, Sundler F. Peptidergic (VIP) innervation of the esophagus. Gastroenterology 1978; 75: 5-8."},{"key":"ref_6","first-page":"1007","article-title":"Distribution of VIP-immunoreactive structures in opossum esophagus","volume":"93","author":"Christensen, J.; Williams, T.H.; Jew, J.; O'Dorisio, T.M.","year":"1987","unstructured":"Christensen J, Williams TH, Jew J, O'Dorisio TM. Distribution of VIP-immunoreactive structures in opossum esophagus. Gastroenterology 1987; 93: 1007-18.","journal-title":"Gastroenterology"},{"key":"ref_7","first-page":"444","article-title":"Calcitonin gene-related peptide immunoreactive sensory and motor nerves of the rat, cat","volume-title":"and monkey esophagus. Gastroenterology 1985; 88","author":"Rodrigo, J.; Polak, J.M.; Fernandez, L.; Ghatei, M.A.; Mulderry, P.; Bloom, SR","unstructured":"Rodrigo J, Polak JM, Fernandez L, Ghatei MA, Mulderry P, Bloom SR. Calcitonin gene-related peptide immunoreactive sensory and motor nerves of the rat, cat, and monkey esophagus. Gastroenterology 1985; 88: 444-51."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1748-1716.1982.tb07101.x","article-title":"Neuronal substance P in the esophagus. Distribution and effects on motor activity","volume":"115","author":"Leander, S.; Erodin, E.; Hakanson, R.; Sundler, F.","year":"1982","unstructured":"Leander S, Erodin E, Hakanson R, Sundler F. Neuronal substance P in the esophagus. Distribution and effects on motor activity. Acta Physiol Scand 1982; 115: 427-35.","journal-title":"Acta Physiol Scand"},{"key":"ref_9","first-page":"517","article-title":"Peptidergic nervous systems in the gut","volume-title":"Clinics in gastroenterology","author":"Sundler, F.; Hakanson, R.; Leander, S.","year":"1980","unstructured":"Sundler F, Hakanson R, Leander S. Peptidergic nervous systems in the gut. In: Costa M, Furness JB, eds. Clinics in gastroenterology. New York: Elsevier, 1980: 517-43."},{"key":"ref_10","first-page":"1363","volume-title":"Distributions of neuropeptides in the human esophagus. Gastroenterology 1987; 93","author":"Wattchow, D.A.; Furness, J.B.; Costa, M.; O'Brien, P.E.; Peacock, M.","unstructured":"Wattchow DA, Furness JB, Costa M, O'Brien PE, Peacock M. Distributions of neuropeptides in the human esophagus. Gastroenterology 1987; 93: 1363-71."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1007\/BF01299816","article-title":"Regulatory peptides in lower esophageal sphincter of pig and man","volume":"31","author":"Aggestrup, S.; Uddman, R.; Jensen, S.L.; Hakanson, R.; Sundler, F.; Muckadell, O.S.","year":"1986","unstructured":"Aggestrup S, Uddman R, Jensen SL, Hakanson R, Sundler F, Muckadell OS, et al. Regulatory peptides in lower esophageal sphincter of pig and man. Dig Dis Sci 1986; 31: 1370-5.","journal-title":"Dig Dis Sci"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/0016-5085(91)90075-V","article-title":"Peptidergic innervation of the human esophageal smooth muscle","volume":"101","author":"Singaram, C.; Sengupta, A.; Sugarbaker, D.J.; Goyal, R.K.","year":"1991","unstructured":"Singaram C, Sengupta A, Sugarbaker DJ, Goyal RK. Peptidergic innervation of the human esophageal smooth muscle. Gastroenterology 1991; 101: 1256-63.","journal-title":"Gastroenterology"},{"key":"ref_13","first-page":"379","article-title":"Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission","volume":"262","author":"Sanders, K.M.; Ward, S.M.","year":"1992","unstructured":"Sanders KM, Ward SM. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol 1992; 262: G379-92.","journal-title":"Am J Physiol"},{"key":"ref_14","first-page":"401","article-title":"Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esohageal muscle","volume":"261","author":"Murray, J.; Du, C.; Ledlow, A.; Bates, J.N.; Conklin, J.L.","year":"1991","unstructured":"Murray J, Du C, Ledlow A, Bates JN, Conklin JL. Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esohageal muscle. Am J Physiol 1991; 261: G401-6.","journal-title":"Am J Physiol"},{"key":"ref_15","first-page":"140","article-title":"Antagonists of nitric oxide synthesis inhibit nerve-mediated relaxations of longitudinal muscle in guinea pig ileum","volume":"260","author":"Osthaus, L.E.; Galligan, J.J.","year":"1992","unstructured":"Osthaus LE, Galligan JJ. Antagonists of nitric oxide synthesis inhibit nerve-mediated relaxations of longitudinal muscle in guinea pig ileum. J Pharmacol Exp Ther 1992; 260: 140-5.","journal-title":"J Pharmacol Exp Ther"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1126\/science.1353273","article-title":"Nitric oxide: first in a new class of neurotransmitters?","volume":"257","author":"Snyder, S.H.","year":"1992","unstructured":"Snyder SH. Nitric oxide: first in a new class of neurotransmitters? Science 1992; 257: 494-6.","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/0024-3205(92)90326-K","article-title":"Role of nitric oxide in lower esophageal sphincter relaxation to swallowing","volume":"50","author":"Yamato, S.; Saha, J.K.; Goyal, R.K.","year":"1992","unstructured":"Yamato S, Saha JK, Goyal RK. Role of nitric oxide in lower esophageal sphincter relaxation to swallowing. Life Sci 1992; 50: 1263-72.","journal-title":"Life Sci"},{"key":"ref_18","first-page":"1012","article-title":"Nitric oxide: mediator of NANC hyperpolarization of opossum esophageal smooth muscle","volume":"261","author":"Du, C.; Murray, J.; Bates, J.N.; Conklin, J.L.","year":"1991","unstructured":"Du C, Murray J, Bates JN, Conklin JL. Nitric oxide: mediator of NANC hyperpolarization of opossum esophageal smooth muscle. Am J Physiol 1991; 261: G1012-6.","journal-title":"Am J Physiol"},{"key":"ref_19","first-page":"695","article-title":"Lu 5, Daniel EE. Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo","volume":"262","author":"Allescher, H.D.; Tougas, G.; Vergara, P.","year":"1992","unstructured":"Allescher HD, Tougas G, Vergara P, Lu 5, Daniel EE. Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo. Am J Physiol 1992; 262: G695-702.","journal-title":"Am J Physiol"},{"key":"ref_20","first-page":"197","article-title":"Yamato 5, Spechler SJ, Goyal RK. Role of nitric oxide in esophageal peristalsis","volume-title":"the opossum. Gastroenterology 1992; 103","unstructured":"Yamato 5, Spechler SJ, Goyal RK. Role of nitric oxide in esophageal peristalsis in the opossum. Gastroenterology 1992; 103: 197-204."},{"key":"ref_21","first-page":"840","article-title":"Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter","volume":"262","author":"Knudsen, M.A.; Svane, D.; Tottrup, A.","year":"1992","unstructured":"Knudsen MA, Svane D, Tottrup A. Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter. Am 7 Physiol 1992; 262: G840-6.","journal-title":"Am 7 Physiol"},{"key":"ref_22","first-page":"385","article-title":"Nitric oxide mediating NANC inhibition in opossum esophageal sphincter","volume":"260","author":"Tottrup, A.; Svane, D.; Forman, A.","year":"1991","unstructured":"Tottrup A, Svane D, Forman A. Nitric oxide mediating NANC inhibition in opossum esophageal sphincter. Am J Physiol 1991; 260: G385-9.","journal-title":"Am J Physiol"},{"key":"ref_23","first-page":"344","article-title":"Effects of transmural field stimulation in isolated muscle strips from human esophagus","volume":"258","author":"Tottrup, A.; Forman, A.; Funch-Jensen, P.; Raundahl, U.; Andersson, K.E.","year":"1990","unstructured":"Tottrup A, Forman A, Funch-Jensen P, Raundahl U, Andersson KE. Effects of transmural field stimulation in isolated muscle strips from human esophagus. Am J Physiol 1990; 258: G344-51.","journal-title":"Am J Physiol"},{"key":"ref_24","first-page":"774","article-title":"Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release","volume":"262","author":"Grider, JR, Murthy; KS, Jin; JG, Makhlouf; G.M.","year":"1992","unstructured":"Grider JR, Murthy KS, Jin JG, Makhlouf GM. Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release. Am J Physiol 1992; 262: G774-8.","journal-title":"Am J Physiol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0014-2999(92)90069-G","article-title":"Nitric oxide synthesis inhibitors attenuate calcitonin gene-related peptide endotheliumdependent vasorelaxation in rat aorta","volume":"212","author":"Gray, D.W.; Marshall, I.","year":"1992","unstructured":"Gray DW, Marshall I. Nitric oxide synthesis inhibitors attenuate calcitonin gene-related peptide endotheliumdependent vasorelaxation in rat aorta. Eur J Pharmacol 1992; 212: 37-42.","journal-title":"Eur J Pharmacol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1476-5381.1992.tb14290.x","article-title":"Mechanism of the vasodilator action of calcitonin generelated peptide in conscious rats","volume":"106","author":"Abdelrahman, A.; Wang, Y.X.; Chang, S.D.; Pang, C.C.","year":"1992","unstructured":"Abdelrahman A, Wang YX, Chang SD, Pang CC. Mechanism of the vasodilator action of calcitonin generelated peptide in conscious rats. Br J Pharmacol 1992; 106: 45-8.","journal-title":"Br J Pharmacol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/BF00270041","article-title":"Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea-pig intestine","volume":"97","author":"Young, H.M.; Furness, J.B.; Shuttleworth, C.W.; Bredt, D.S.; Snyder, S.H.","year":"1992","unstructured":"Young HM, Furness JB, Shuttleworth CW, Bredt DS, Snyder SH. Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea-pig intestine. Histochemistry 1992; 97: 375-8.","journal-title":"Histochemistry"},{"key":"ref_28","first-page":"231","article-title":"Mucosal peptidergic innervation of the opossum esophagus and anal canal: a comparison with snout skin. J7 Auton Nerv Syst","volume":"29","author":"Singaram, C.; Sengupta, A.; Spechler, S.J.; Goyal, R.K.","year":"1990","unstructured":"Singaram C, Sengupta A, Spechler SJ, Goyal RK. Mucosal peptidergic innervation of the opossum esophagus and anal canal: a comparison with snout skin. J7 Auton Nerv Syst 1990; 29: 231-40."},{"key":"ref_29","first-page":"7797","article-title":"Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain","volume-title":"and peripheral tissues. Proc Natl Acad Sci","volume":"88","author":"Dawson, T.M.; Bredt, D.S.; Fotuhi, M.; Hwang, P.M.; Snyder, S.H.","year":"1991","unstructured":"Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci 1991; 88: 7797-801."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1073\/pnas.88.7.2811","article-title":"Neuronal NADPH diaphorase is a nitric oxide synthase","volume":"88","author":"Hope, B.T.; Michael, G.J.; Knigge, K.M.; Vincent, SR","year":"1991","unstructured":"Hope BT, Michael GJ, Knigge KM, Vincent SR. Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci 1991; 88: 2811-4.","journal-title":"Proc Natl Acad Sci"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/0896-6273(91)90374-9","article-title":"Nitric oxide synthase protein and mRNA are discretely localized in mammalian CNS together with NADPH diaphorase","volume":"7","author":"Bredt, D.S.; Glatt, C.E.; Hwang, P.M.; Fotuhi, M.; Dawson, T.M.; Snyder, S.H.","year":"1991","unstructured":"Bredt DS, Glatt CE, Hwang PM, Fotuhi M, Dawson TM, Snyder SH. Nitric oxide synthase protein and mRNA are discretely localized in mammalian CNS together with NADPH diaphorase. Neuron 1991; 7: 615-24.","journal-title":"Neuron"},{"key":"ref_32","first-page":"1901","article-title":"Development profile of neuron-specific enolase in human gut and its implications","volume-title":"Hirschsprung's disease. Gastroenterology 1986; 90","author":"Tam, P.K.; Lister, J.","unstructured":"Tam PK, Lister J. Development profile of neuron-specific enolase in human gut and its implications in Hirschsprung's disease. Gastroenterology 1986; 90: 1901-6."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/BF01899135","article-title":"Detection of nerve cells by a histochemical technic","volume":"25","author":"Gabella, G.","year":"1969","unstructured":"Gabella G. Detection of nerve cells by a histochemical technic. Expenentia 1969; 25: 218-9.","journal-title":"Expenentia"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.35.12.1690","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:06:29Z","timestamp":1764993989000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.35.12.1690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,12]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1994,12,1]]},"published-print":{"date-parts":[[1994,12]]}},"alternative-id":["10.1136\/gut.35.12.1690"],"URL":"https:\/\/doi.org\/10.1136\/gut.35.12.1690","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,12]]}}}