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 colorecturn. This study investigated whether purinergic signaling contributes to mechanosensory transduction in the rat colorecturn. 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: P2X3 receptor immunostaining was present on subpopulations of neurons in L1 and S1 dorsal root ganglia, which supply the rat colorecturn. 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'-tri phosphate, 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'-tri phosphate, suggesting a correlation between purinergic activation and nociceptive stimuli. Conclusions: Adenosine 5'-triphosphate contributes to mechanosensory transduction in the rat colorecturn, and this is probably associated with pain.