Novel capsaicin (VR1) and purinergic (P2X3) receptors in Hirschsprung's intestine

J Pediatr Surg. 2001 Nov;36(11):1679-84. doi: 10.1053/jpsu.2001.27959.


Background/purpose: Studies of Hirschsprung's disease (HSCR) have shown that hypertrophic nerves in aganglionic bowel are mainly of extrinsic origin and may contain sensory elements. Recent advances have shown a specific capsaicin receptor VR1 (vanilloid receptor-1), and an ATP-gated ion channel P2X(3), which are expressed by sensory neurons.

Methods: This study investigated, for the first time, the distribution of VR1- and P2X(3)-immunoreactivity in normal adult, infant, and HSCR large intestine, using specific antibodies for immunohistochemistry.

Results: VR1-immunoreactive fibers and nerve fascicles, but not somata, were detected in all regions of the bowel in controls with few weakly immunostained fibers in the mucosa/lamina propria. Hypertrophic nerve bundles in hypoganglionic and aganglionic bowel showed intense VR1-immunoreactivity, whereas normoganglionic regions of HSCR were similar to controls. P2X(3)-immunoreactive neuronal cell bodies, in some instances with long axonal processes, were detected in the myenteric and submucous plexuses in control infant, adult, and ganglionic HSCR samples. Aganglionic samples showed weak P2X(3)-immunoreactivity in hypertrophic nerve fasciculi in the submucous and myenteric plexuses.

Conclusions: The presence of VR1- and P2X(3)-immunoreactivities in aganglionic HSCR bowel indicates that sensory nerves may form a significant proportion of its hypertrophic innervation. The functional significance of P2X(3) and VR1 receptors in enteric nerves deserves further investigation.

MeSH terms

  • Case-Control Studies
  • Female
  • Hirschsprung Disease / metabolism*
  • Humans
  • Hypertrophy / metabolism
  • Infant
  • Intestine, Large / innervation
  • Intestine, Large / metabolism*
  • Male
  • Neurons / metabolism*
  • Neurons / pathology
  • Receptors, Drug / metabolism*
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X3


  • P2RX3 protein, human
  • Receptors, Drug
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X3