Purinergic mechanisms contribute to mechanosensory transduction in the rat colorectum.

BACKGROUND & AIMS Adenosine 5'-triphosphate plays a role in peripheral sensory mechanisms and, in particular, mechanosensory transduction in the urinary system. P2X(3) receptors are selectively expressed on small-diameter sensory neurons in the dorsal root ganglia; sensory neurons from dorsal root ganglia L1 and S1 supply the colorectum. This study investigated whether purinergic signaling contributes to mechanosensory transduction in the rat colorectum. METHODS A novel in vitro rat colorectal preparation was used to elucidate whether adenosine 5'-triphosphate is released from the mucosa in response to distention and to evaluate whether it contributes to sensory nerve discharge during distention. RESULTS P2X(3) receptor immunostaining was present on subpopulations of neurons in L1 and S1 dorsal root ganglia, which supply the rat colorectum. Distention of the colorectum led to pressure-dependent increases in adenosine 5'-triphosphate release from colorectal epithelial cells and also evoked pelvic nerve excitation, which was mimicked by application of adenosine 5'-triphosphate and alpha,beta-methylene adenosine 5'-triphosphate. The sensory nerve discharges evoked by distention were potentiated by alpha,beta-methylene adenosine 5'-triphosphate and ARL-67156, an adenosine triphosphatase inhibitor, and were attenuated by the selective P2X(1), P2X(3), and P2X(2/3) antagonist 2',3'-O-trinitrophenyl-adenosine 5'-triphosphate and by the nonselective P2 antagonists pyridoxyl 5-phosphate 6-azophenyl-2',4'-disulfonic acid and suramin. Adenosine, after ectoenzymatic breakdown of adenosine 5'-triphosphate, seems to be involved in the longer-lasting distention-evoked sensory discharge. Single-fiber analysis showed that high-threshold fibers were particularly affected by alpha,beta-methylene adenosine 5'-triphosphate, suggesting a correlation between purinergic activation and nociceptive stimuli. CONCLUSIONS Adenosine 5'-triphosphate contributes to mechanosensory transduction in the rat colorectum, and this is probably associated with pain.