Novel capsaicin (VR1) and purinergic (P2X3) receptors in Hirschsprung's intestine☆
Section snippets
HSCR and control patients
Full-thickness, surgically resected colonic tissues were obtained from 8 patients with approval from the local ethics committee. All patients had sporadic distal colonic or short-segment-disease without clinical evidence of an established major genetic syndrome, eg, Down's syndrome/Shah-Waardenburg syndrome (6 male, 2 female, age 0.2 to 1.0 years). Specimens were taken from aganglionic and normoganglionic regions on the basis of histologic characterization. Age-matched control tissues were
VR1
In control tissues, VR1 immunoreactivity was detected in nerve fascicles in the myenteric plexus with fibers in the muscle layers (Fig 1a).
Discussion
The basic neural reflex circuit for normal peristalsis consists of sensory neurons, interneurons and motor neurons. Afferent nerves carry impulses generated by bowel wall distension and chemical or mechanical irritation of bowel mucosa to activate interneurons that stimulate motor excitatory neurons proximally and inhibitory neurons distally.16 VR1 and P2X3 are novel receptors of subsets of nociceptive sensory neurons. Our finding of VR1-and P2X3-immunoreactive nerves in the myenteric and
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ATP (P2X) receptors and pain
Cited by (51)
P2X3 receptors participate in purinergic inhibition of gastrointestinal smooth muscle
2021, Autonomic Neuroscience: Basic and ClinicalThe Role of TRPV1 in Acquired Diseases: Therapeutic Potential of TRPV1 Modulators. Therapeutic Potential of TRPV1 Modulators.
2015, TRP Channels as Therapeutic Targets: From Basic Science to Clinical UseThe role of purinergic pathways in the pathophysiology of gut diseases: Pharmacological modulation and potential therapeutic applications
2013, Pharmacology and TherapeuticsCitation Excerpt :Subsequent investigations evaluated the patterns of purinergic receptor expression in colonic tissues from patients with Hirschsprung's disease. Facer et al. (2001) showed that the expression of P2X3 receptors in aganglionic colonic samples was reduced. Then, O' Donnell and Puri (2008) observed that the expression of P2Y1 and P2Y2 receptors was also decreased in the colon of patients with Hirschsprung's disease, suggesting an unsettled ATP neurotransmission which might contribute to the condition of persistent contraction occurring in the aganglionic gut of these patients.
Roles of substance P and ATP in the subepithelial fibroblasts of rat intestinal villi
2013, International Review of Cell and Molecular BiologyCitation Excerpt :However, extrinsic spinal afferents can certainly form close contacts with subepithelial fibroblasts. In the aganglionic bowel, enteric nerves are decreased or absent, and VR-1 and P2X3-IR extrinsic spinal afferent nerve fivers are hyperinnervated (Facer et al., 2001). The amount of synapse-like structures between the subepithelial fibroblasts and nerve varicosities in the mucosa was markedly increased (Nagahama et al., 2001).
Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system
2011, Pharmacology and TherapeuticsCitation Excerpt :In fact, the majority of nodose ganglion neurons projecting to the rodent stomach and of DRG neurons projecting to the rodent gut express TRPV1 (Robinson et al., 2004; Schicho et al., 2004; Zhang et al., 2004; Brierley et al., 2005; Hwang et al., 2005; Christianson et al., 2006a, 2006b; Tan et al., 2008; Zhong et al., 2008), while only 32% of the vagal afferent neurons supplying the murine jejunum contain TRPV1 (Tan et al., 2009). Within the rodent and human alimentary canal, TRPV1-positive nerve fibers occur in the musculature, enteric nerve plexuses, arterioles and mucosa (Facer et al., 2001; Yiangou et al., 2001; Chan et al., 2003; Patterson et al., 2003; Ward et al., 2003; Holzer, 2004; Horie et al., 2004; Kadowaki et al., 2004; Matthews et al., 2004; Robinson et al., 2004; Schicho et al., 2004; Zhang et al., 2004; Faussone-Pellegrini et al., 2005; Bhat & Bielefeldt, 2006; Akbar et al., 2008; Matsumoto et al., 2009, 2011). In addition, TRPV1 is present in nerve fibers supplying the taste papillae of the tongue (Caterina et al., 1997; Tominaga et al., 1998; Ishida et al., 2002; DeSimone & Lyall, 2006).
P2X Receptors in Health and Disease
2011, Advances in PharmacologyCitation Excerpt :Chronic functional visceral hyperalgesia induced in a rat model of IBS is associated with potentiation of ATP-evoked responses and an enhanced expression of P2X3 receptors in colon-specific sensory neurons (Xu et al., 2008). P2X3 immunohistochemistry has been demonstrated in aganglionic bowel in Hirschsprung's disease, suggesting that the sensory nerves may form a significant proportion of its hypertrophic innervation (Facer et al., 2001). Intrinsic sensory neurones in the submucous plexus of the gut, as well as extrinsic sensory nerves, show positive immunoreactivity for P2X3 receptors (Xiang & Burnstock, 2004).
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Address reprint requests to Professor Praveen Anand, Peripheral Neuropathy Unit, Imperial College School of Medicine, Hammersmith Hospital, London, England, or Professor Paul K.H. Tam, Department of Surgery, University of Hong Kong Medical Center, Queen Mary Hospital, Hong Kong SAR, China.