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.