P2X purinoceptor-induced sensitization of ferret vagal mechanoreceptors in oesophageal inflammation.
1. Using an in vitro single unit recording technique we studied the changes in mechanical and chemical sensitivity of vagal afferent fibres in acute oesophagitis, with particular attention to inflammatory products such as purines. 2. Histologically verified oesophagitis was induced by oesophageal perfusion of 1 mg ml-1 pepsin in 150 mM HCl in anaesthetized ferrets for 30 min on two consecutive days. Controls were infused with 154 mM NaCl. 3. The number of action potentials evoked in oesophageal mucosal afferents by mucosal stroking with calibrated von Frey hairs (10-1000 mg) was stimulus dependent. In oesophagitis responsiveness was reduced across the range of stimuli compared with controls. 4. Topical application of the P2X purinoceptor agonist alphabeta-methylene ATP had no direct excitatory effect on afferents. In oesophagitis, but not in controls, there was a significant increase in responses to stroking with von Frey hairs during superfusion with alphabeta-methylene ATP (1 microM). 5. Mucosal afferents responded directly to one or more chemical stimuli: 26 % (5/19 afferents) responded in controls, and 47 % (7/15 afferents) in oesophagitis. There were no differences in responsiveness to bradykinin (1 microM), prostaglandin E2 (100 microM), 5-hydroxytryptamine (100 microM), capsaicin (1 mM) or hydrochloric acid (150 mM) between control and oesophagitis groups. 6. We conclude that a sensitizing effect of a P2X purinoceptor agonist on mechanosensory function is induced in oesophagitis. This effect is offset by a decrease in basal mechanosensitivity.
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Nerve-Gut Research Laboratory, Department of Gastrointestinal Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia.
O'Donnell
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Blackshaw
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004942:Esophagitis, Peptic / Q000139:chemically induced / Q000378:metabolism*; D004947:Esophagus / Q000294:innervation / Q000378:metabolism*; D005289:Ferrets; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism*; D009092:Mucous Membrane / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009431:Neural Conduction / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D010434:Pepsin A; D010812:Physical Stimulation; D058910:Purinergic P2 Receptor Agonists; D011930:Reaction Time / Q000187:drug effects; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D014630:Vagus Nerve / Q000378:metabolism*
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D010434:Pepsin A; C002630:alpha,beta-methyleneadenosine 5'-triphosphate