Purinergic mechanisms contribute to mechanosensory transduction in the rat colorectum

Abstract

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 α,β-methylene adenosine 5′-triphosphate. The sensory nerve discharges evoked by distention were potentiated by α,β-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 α,β-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.