Abstract
Hirschsprung’s disease is characterized by the absence of ganglion cells in the distal bowel and extends proximally for varying distances. In recent years, the purinergic P2Y receptors have begun to receive much attention as they have been recognised as major ATP receptors in many regions of the body, including the intestine. ATP has long been established as an inhibitory neurotransmitter in the enteric nervous system. The aim of our study was to analyse the expression of P2Y1 and P2Y2 receptors in the intestine of patients with Hirschsprung’s disease. Frozen sections were cut from rectal tissue segments taken from both the aganglionic and ganglionic regions of patients with Hirschsprung’s disease, as well as tissue from normal rectal biopsies, which were used as controls. Sections were incubated overnight with P2Y1 and P2Y2 receptor antibodies and results were analysed by light microscopy. Both P2Y1 and P2Y2 immunoreactivity was absent from the submucosal and myenteric plexuses of aganglionic tissue compared to ganglionic tissue and normal controls, in which large number of immunoreactive neurons were evident, arranged in ganglia in both plexuses and positive nerve fibres, in both the smooth and circular muscles. Our results show a lack of expression of P2Y1 and P2Y2 receptors in the aganglionic gut in Hirschsprung’s disease. The absence of these receptors suggests the absence of the inhibitory neurotransmitter ATP, which may help to explain the contracted state of the aganglionic gut in Hirschsprung’s disease.
Similar content being viewed by others
References
Newgreen D, Young HM (2002) Enteric nervous system: development and developmental disturbances-part 1. Pediatr Dev Pathol 5:224–247
Kleinhaus S, Boley SJ, Sheran M (1979) Hirschsprung’s disease: a survey of the surgical section of the American Academy of Pediatrics. J Pediatr Surg 14:588–597
Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492
Burnstock G (2004) Introduction: P2 receptors. Curr Top Med Chem 4:793–803
Burnstock G (1972) Purinergic nerves. Pharmacol Rev 34:509–581
Van Nassauw L, Costagliola A, Van Op den Bosch J et al (2006) Region-specific distribution of the P2Y4 receptor in enteric glial cells and interstitial cells of Cajal within the guinea-pig gastrointestinal tract. Auton Neurosci 127:299–306
Gallego D, Hernandez P, Clave P et al (2006) P2Y1 receptors mediate inhibitory purinergic neuromuscular transmission in the human colon. Am J Physiol Gastrointest Liver Physiol 291:G584–G594
Tsuto T, Okamura H, Fukui K (1982) An immunohistochemical investigation of vasoactive intestinal polypeptide in the colon of patients with Hirschsprung’s disease. Neurosci Lett 34:57–62
Bealer J, Natuzzi E, Buscher C (1994) Nitric oxide synthase is deficient in the aganglionic colon of patients with Hirschsprung’s disease. Pediatrics 93:647–651
Vanderwinden JM, De Laet MH, Schiffman SN et al (1993) Nitric oxide synthase distribution in the enteric nervous system in Hirschsprung’s disease. Gastroenterology 105:969–973
Tomita R, Munakata K, Kurosu Y (1994) Peptidergic nerves in Hirschsprung’s disease and its allied disorders. Eur J Pediatr Surg 4:346–351
Kobayashi H, O’Briain D, Puri P (1994) Lack of expression of NADPH-diaphorase and neural cell adhesion molecule (NCAM) in colonic muscle of patients with Hirschsprung’s disease. J Pediatr Surg 29:301–304
Kusafuka T, Puri P (1997) Altered mRNA expression of the neuronal nitric oxide synthase gene in Hirschsprung’s disease. J Pediatr Surg 32:1054–1058
Nemeth L, Puri P (2001) Three-dimensional morphology of c-Kit-positive cellular network and nitrergic innervation in the human gut. Arch Pathol Lab Med 125:899–904
Tomita R (1995) A role of nitric oxide in Hirschsprung’s disease. J Pediatr Surg 30:437–440
Larsson L, Sundler F (1990) Neuronal markers in Hirchsprung’s disease with special reference to neuropeptides. Acta Histochem Suppl 38:115–125
Brookes SJ, Costa M (1990) Identification of enteric motor neurons which innervate the circular muscle of the guinea-pig small intestine. Neurosci Lett 118:227–230
Wang G, Wang X, Hu H et al (2007) Inhibitory neuromuscular neurotransmission mediated by the P2Y1 purinergic receptor in the guinea-pig small intestine. Am J Physiol Gastrointest Liver Physiol 292:G1483–G1489
Fang X, Hu H, Gao N et al (2006) Neurogenic secretion mediated by the purinergic P2Y1 receptor in guinea-pig small intestine. Eur J Pharmacol 536:113–122
Fie G, Fang X, Wang X et al (2006) Neurogenic mucosal bicarbonate secretion mediated by the purinergic P2Y1 receptor in guinea-pig duodenum. Gastroenterology 130:A380
Burnstock G (2007) Purine and pyrimidine receptors. Cell Mol Life Sci 64:1471–1483
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
O’ Donnell, AM., Puri, P. Deficiency of purinergic P2Y receptors in aganglionic intestine in Hirschsprung’s disease. Pediatr Surg Int 24, 77–80 (2008). https://doi.org/10.1007/s00383-007-2044-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00383-007-2044-1