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Extracellular single fiber recordings of activity originating in C-fiber terminals were made in the ex vivo vagally innervated guinea pig esophagus. The adenosine A<jats:sub>2A<\/jats:sub>receptor-selective agonist CGS21680 induced robust, reversible sensitization of the response to esophageal distention (10\u201360 mmHg) in a concentration-dependent fashion (1\u2013100 nM). At the half-maximally effective concentration (EC<jats:sub>50<\/jats:sub>: \u22483 nM), CGS21680 induced an approximately twofold increase in the mechanical response without causing an overt activation. This sensitization was abolished by the selective A<jats:sub>2A<\/jats:sub>antagonist SCH58261. The adenylyl cyclase activator forskolin mimicked while the nonselective protein kinase inhibitor H89 inhibited mechanical sensitization by CGS21680. CGS21680 did not enhance the response to the purinergic P2X receptor agonist \u03b1,\u03b2-methylene-ATP, indicating that CGS21680 does not nonspecifically sensitize to all stimuli. Mechanical sensitization by CGS21680 was abolished by pretreatment with two structurally different TRPA1 antagonists AP18 and HC030031 . Single cell RT-PCR and whole cell patch-clamp studies in isolated esophagus-specific nodose neurons revealed the expression of TRPA1 in A<jats:sub>2A<\/jats:sub>-positive C-fiber neurons and demonstrated that CGS21682 potentiated TRPA1 currents evoked by allylisothiocyanate. We conclude that stimulation of the adenosine A<jats:sub>2A<\/jats:sub>receptor induces mechanical sensitization of nodose C fibers by a mechanism sensitive to TRPA1 antagonists indicating the involvement of TRPA1.<\/jats:p>","DOI":"10.1152\/ajpgi.00350.2014","type":"journal-article","created":{"date-parts":[[2015,11,13]],"date-time":"2015-11-13T02:48:40Z","timestamp":1447382920000},"page":"G215-G223","source":"Crossref","is-referenced-by-count":13,"title":["Mechanisms of the adenosine A<sub>2A<\/sub>receptor-induced sensitization of esophageal C fibers"],"prefix":"10.1152","volume":"310","author":[{"given":"M.","family":"Brozmanova","sequence":"first","affiliation":[{"name":"Department of Pathophysiology and Biomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Mazurova","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology 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