Abstract | BACKGROUND: AIMS: To examine the role of P2XR signalling in the pathogenesis in a rat model of IBS-like visceral hyperalgesia. METHODS: Visceral hypersensitivity was induced by colonic injection of 0.5% acetic acid (AA) in 10-day-old rats and experiments were conducted at 8 weeks of age. Dorsal root ganglion (DRG) neurons innervating the colon were labelled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) fluorescence into the colon wall. RESULTS: Visceral hypersensitivity was reversed by TNP-ATP (2'-(or-3')-O-(trinitrophenyl) ATP), a potent P2X1, P2X3 and P2X2/3 receptor antagonist. Rapid application of ATP (20 microM) induced a fast inactivating current in colon-specific DRG neurons from both control and AA-treated rats. There was a twofold increase in the peak ATP responses in neurons from AA-treated rats. These currents were sensitive to TNP-ATP (100 nM). Under current-clamped conditions, ATP evoked a larger membrane depolarisation in neurons from neonatal AA-treated rats than in controls. P2X3R protein expression was significantly enhanced in colon-specific DRGs 8 weeks after neonatal AA treatment. CONCLUSIONS: These data suggest that the large enhancement of P2XR expression and function may contribute to the maintenance of visceral hypersensitivity, thus identifying a specific neurobiological target for the treatment of chronic visceral hyperalgesia.
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Authors | G-Y Xu, M Shenoy, J H Winston, S Mittal, P J Pasricha |
Journal | Gut
(Gut)
Vol. 57
Issue 9
Pg. 1230-7
(Sep 2008)
ISSN: 1468-3288 [Electronic] England |
PMID | 18270243
(Publication Type: Journal Article)
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Chemical References |
- Purinergic P2 Receptor Antagonists
- Receptors, Purinergic P2
- Receptors, Purinergic P2X
- 2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate
- Adenosine Triphosphate
- Acetic Acid
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Topics |
- Acetic Acid
- Adenosine Triphosphate
(analogs & derivatives, pharmacology)
- Animals
- Chronic Disease
- Colon
(innervation)
- Disease Models, Animal
- Hyperalgesia
(chemically induced, physiopathology)
- Irritable Bowel Syndrome
(chemically induced, physiopathology)
- Membrane Potentials
(drug effects)
- Neurons
(drug effects, physiology)
- Patch-Clamp Techniques
- Purinergic P2 Receptor Antagonists
- Rats
- Rats, Sprague-Dawley
- Receptors, Purinergic P2
(physiology)
- Receptors, Purinergic P2X
- Signal Transduction
- Up-Regulation
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