ATP contributes to mechanosensory transduction in the rat colorectum. P2X3 receptors are present on dorsal root ganglia (DRG) neurons that supply this area of the gut. Previous studies have shown an increased role for
ATP in inflamed tissues. We aimed to investigate whether an increased purinergic component exists during mechanosensory transduction in a rat model of
colitis. An in vitro rat colorectal preparation was used to investigate whether distension increased
ATP release and to evaluate the role of
purinergic antagonists in distension-evoked sensory discharges in the pelvic nerve in normal and
colitis preparations. DRG neuron
purinoceptors were also studied. Distension-evoked responses in the
colitis model were attenuated to a significantly greater extent by 2',3'-O-trinitrophenyl-ATP and pyridoxyl 5-phosphate 6-azophenyl-2',4'-disulfonic
acid.
Inflammation caused augmented distension-evoked sensory nerve excitation after application of
ATP and
alpha,beta-methylene ATP. Single-fiber analysis confirmed that mean firing per unit was increased. Distension-evoked increases in
ATP release from epithelial cells were substantially higher. The number of DRG neurons responding to
ATP and the number of those staining for the
P2X3 receptor, particularly those containing
calcitonin gene-related peptide, were increased.
Adenosine, after ectoenzymatic breakdown of
ATP, is involved to a lesser degree in the longer-lasting distension-evoked sensory discharge, suggesting reduced
ATPase activity. It was therefore concluded that
ATP has an enhanced role in mechanosensory transduction in the inflamed rat colorectum. The underlying mechanisms appear to involve increased distension-evoked release of
ATP as well as an increase in the number of DRG neurons supplying the colorectum expressing P2X3 receptors, especially those containing
calcitonin gene-related peptide.