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.[1]References
- Purinergic mechanisms contribute to mechanosensory transduction in the rat colorectum. Wynn, G., Rong, W., Xiang, Z., Burnstock, G. Gastroenterology (2003) [Pubmed]
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