Abstract
Nitric oxide (NO) has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic (NANC) inhibitory nerves in the gastrointestinal tract. To clarify the the role of NO in the human lower esophageal sphincter (LES), enteric nerve responses in lower esophageal tissue specimens obtained from patients with esophageal cancer (n=7) and patients with gastric cancer (n=6) were investigated. A mechanographic technique was used to evaluate in vitro LES muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, including NG-nitro-L-arginine (L-NNA) and L-arginine. Findings were: (1) Cholinergic nerves were those mainly involved in the regulation of enteric nerve responses to EFS in the steady state, and NANC inhibitory nerves acted on the LES; (2) L-NNA concentration-dependently inhibited the relaxation in response to EFS in the LES; and (3) this inhibitory effect in the LES was reversed by L-arginine. These findings suggest that cholinergic and NANC inhibitory nerves play important roles in regulating contraction and relaxation of the human LES, and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of the human LES.
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References
Li Q, Castell JA, Castell DD. Manometric determination of esophageal length. Am J Gastroenterol 1994;89:722–725.
Furness JB, Costa M. The nervous release and action of sub-stances which affect intestinal muscle through neither adrenoreceptors nor cholinoreceptors. Philos Trans R Soc Lond Biol 1973;265:123–133.
Tomita R, Kurosu Y, Aoki N, Tanjoh K, Munakata K. Study on non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with diverticular disease. Nihon Univ J Med 1993;35:15–21.
Tomita R, Munakata K, Aoki N, Tanjoh K, Abe Y, Kurosu Y. Regulation of non-adrenergic non-cholinergic inhibitory nerves in the colonie segment of elongated sigmoid colon. Nihon Univ J Med 1995;37:l-6.
Goyal RK, Paterson WG. Esophageal motility. In: Schultz SG, Wood JD, Rauner BB (eds). Handbook of physiology. Section 6: The gastrointestinal system. Bethesda, Maryland: American Physiological Society, 1989;865–908.
Diamant NE. Physiology of esophageal motor function. Gastroenterol Clin North Am 1989;18:179–194.
Grider JR Makhlouf GM. Vasoactive intestinal peptide. Acad Sci 1988;527:369–377.
Burleigh DE. NG-nitro-L-arginine reduces nonadrenergic noncholinergic relaxation of human gut. Gastroenterology 1992;102:679–683.
Stark ME, Szurszewski JH. Role of nitric oxide in gastrointestinal and hepatic function and disease. Gastroenterology 1992;103:1928–1949.
Tomita R, Munakata K, Kurosu Y, Tanjoh K. A role of nitric oxide in Hirschsprung's disease. J Pediatr Surg 1995;30:437–440.
Alm P, Larsson B, Anderson KE. NADPH diaphorase activity and non-adrenergic non-cholinergic relaxation of the human gastrointestinal tract. Acta Physiol Scand 1992;146:285–287.
Munakata K, Tomita R, Kurosu Y. Histologic studies on neuronal intestinal dysplasia and Hirschsprung's disease with special reference to NADPH-diaphorase. Biomed Res 1994;15:205–211.
Preikisaitis HG, Tremblay L, Diamant N. Nitric oxide mediates inhibitory nerve effects in human esophagus and lower esophageal sphincter. Dig Dis Sci 1994;39:770–775.
Paricha PJ, Rarich WJ, Kallo AN. Effects of intrasphincteric botulinum toxin on the lower esophageal sphincter in piglets. Gastroenterology 1993;105:1045–1049.
Bult H, Boeckxstaens GE, Pelckmans PA. Nitric oxide as an inhibition non-adrenergic non-cholinergic neurotransmitter. Nature 1990;345:346–347.
Richards WG, Kobzik L, Stamler J, et al. Distribution of nitric oxide synthase in the human esophagus. Gastroenterology 1993;104:571–572.
Christensen J. Motor functions of pharynx and esophagus. In: Johnson LR (ed) Physiology of the gastrointestinal tract. New York: Raven 1993;595–612.
Grider JR. Identification of neurotransmitters regulating intesti-nal peristaltic reflex in humans. Gastroenterology 1989;97:1414–1419.
Tomita R Kurosu Y, Munakata K, Aoki N, Tanjoh K. Physiological studies on gastrointestinal hormones in the colon of patients with diverticular disease. Nihon Univ J Med 1993;35:253–259.
Tomita R, Munakata K, Kurosu Y. Peptidergic nerves in Hirschsprung's disease and its allied disorders. Eur J Pediatr Surg 1994;4:346–351.
Tomita R, Munakata K, Tanjoh K, Kurosu Y. Regulation of the enteric nervous system and innervation of the peptidergic nerve in the colonie segment of elongated sigmoid colon. Biomed Res 1994;15:195–201.
Stark ME, Bauer AJ, Sarr MG. Nitric oxide mediates inhibitory nerve input in human and canine jejunum. Gastroenterology 1993;104:398–409.
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Tomita, R., Kurosu, Y. & Munakata, K. Relationship between nitric oxide and non-adrenergic non-cholinergic inhibitory nerves in human lower esophageal sphincter. J Gastroenterol 32, 1–5 (1997). https://doi.org/10.1007/BF01213288
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DOI: https://doi.org/10.1007/BF01213288