{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:33:02Z","timestamp":1773325982784,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,5,3]],"date-time":"2013-05-03T00:00:00Z","timestamp":1367539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p><jats:p>Nitric oxide is a strong modulator of carotid body (CB) chemoreceptor activity; however, the mechanisms leading to the production\/release of NO during CB chemoexcitation remained largely unknown.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and what is its importance?<\/jats:bold><\/jats:p><jats:p>In the present study, we identified an important contribution of ATP and purinergic P2X receptor signalling in initiating the events leading to NO synthesis and release in efferent neurons to the CB. Acting via P2X receptors, ATP causes an increase in intracellular Ca<jats:sup>2+<\/jats:sup> that triggers NO production in efferent neurones to the rat carotid body. In addition, ATP\u2010induced depolarization of these neurones activates voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> channels that further amplify the NO inhibitory signal.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>The mammalian carotid body (CB) is a peripheral chemosensory organ that controls ventilation and is innervated by both afferent and efferent nerve fibres. The afferent pathway is stimulated by chemoexcitants, such as hypoxia, hypercapnia and acidosis. The efferent pathway causes inhibition of the sensory discharge via release of NO that originates mainly from neuronal nitric oxide synthase (nNOS)\u2010positive autonomic neurones within the glossopharyngeal nerve (GPN). Recent studies in the rat indicate that these inhibitory GPN neurones and their processes express purinergic P2X receptors and can be activated by ATP, a key excitatory CB neurotransmitter. Here we tested the hypothesis that purinergic agonists stimulate a rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, leading to nNOS activation and NO production in isolated GPN neurones, using the fluorescent probes fura\u20102 and 4\u2010amino\u20105\u2010methylamino\u20102\u2032,7\u2032\u2010difluorofluorescein diacetate (DAF\u2010FM DA), respectively. ATP caused a dose\u2010dependent increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in GPN neurones (EC<jats:sub>50<\/jats:sub>\u2248 1.92 \u03bc<jats:sc>m<\/jats:sc>) that was markedly inhibited by a combination of 100 \u03bc<jats:sc>m<\/jats:sc> suramin (a non\u2010specific P2X blocker) and 100 n<jats:sc>m<\/jats:sc> Brilliant Blue G (a selective P2X7 blocker). ATP also stimulated NO production in GPN neurones, as revealed by an increase in DAF fluorescence; this NO signal was inhibited by purinergic blockers, chelators of extracellular Ca<jats:sup>2+<\/jats:sup>, the nNOS inhibitor <jats:sc>l<\/jats:sc>\u2010NAME and the NO scavenger carboxy\u2010PTIO. The P2X2\/3 and P2X7 agonists \u03b1,\u03b2,\u2010methylene ATP and benzoyl ATP mimicked the effects of ATP. Taken together, these data indicate that ATP may contribute to negative feedback inhibition of CB sensory discharge via purinergic stimulation of NO production in efferent fibres.<\/jats:p>","DOI":"10.1113\/expphysiol.2013.072058","type":"journal-article","created":{"date-parts":[[2013,3,23]],"date-time":"2013-03-23T02:17:06Z","timestamp":1364005026000},"page":"1199-1212","source":"Crossref","is-referenced-by-count":8,"title":["Purinergic stimulation of carotid body efferent glossopharyngeal neurones increases intracellular Ca<sup>2+<\/sup> and nitric oxide production"],"prefix":"10.1113","volume":"98","author":[{"given":"Michael","family":"Lowe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Jin","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin 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