Purinergic component of mechanosensory transduction is increased in a rat model of colitis.
ATP contributes to mechanosensory transduction in the rat colorectum. P2X3 receptors are present on dorsal root ganglia (DRG) neurons that supply this area of the gut. Previous studies have shown an increased role for ATP in inflamed tissues. We aimed to investigate whether an increased purinergic component exists during mechanosensory transduction in a rat model of colitis. An in vitro rat colorectal preparation was used to investigate whether distension increased ATP release and to evaluate the role of purinergic antagonists in distension-evoked sensory discharges in the pelvic nerve in normal and colitis preparations. DRG neuron purinoceptors were also studied. Distension-evoked responses in the colitis model were attenuated to a significantly greater extent by 2',3'-O-trinitrophenyl-ATP and pyridoxyl 5-phosphate 6-azophenyl-2',4'-disulfonic acid. Inflammation caused augmented distension-evoked sensory nerve excitation after application of ATP and alpha,beta-methylene ATP. Single-fiber analysis confirmed that mean firing per unit was increased. Distension-evoked increases in ATP release from epithelial cells were substantially higher. The number of DRG neurons responding to ATP and the number of those staining for the P2X3 receptor, particularly those containing calcitonin gene-related peptide, were increased. Adenosine, after ectoenzymatic breakdown of ATP, is involved to a lesser degree in the longer-lasting distension-evoked sensory discharge, suggesting reduced ATPase activity. It was therefore concluded that ATP has an enhanced role in mechanosensory transduction in the inflamed rat colorectum. The underlying mechanisms appear to involve increased distension-evoked release of ATP as well as an increase in the number of DRG neurons supplying the colorectum expressing P2X3 receptors, especially those containing calcitonin gene-related peptide.
Autonomic Neuroscience Institute, Royal Free and University College School of Medicine, London NW3 2PF, United Kingdom.
Gregory
G
Wynn
Bei
B
Ma
Huai Zhen
HZ
Ruan
Geoffrey
G
Burnstock
D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003092:Colitis / Q000503:physiopathology*; D003106:Colon / Q000294:innervation / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010388:Pelvis / Q000294:innervation; D010812:Physical Stimulation; D011312:Pressure; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D012007:Rectum / Q000294:innervation / Q000502:physiology
C546403:P2rx2 protein, rat; C546410:P2rx3 protein, rat; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D015740:Calcitonin Gene-Related Peptide