{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:08:08Z","timestamp":1789992488428,"version":"4.0.1"},"reference-count":57,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2009,11,10]],"date-time":"2009-11-10T00:00:00Z","timestamp":1257811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2009,11,15]]},"abstract":"<jats:p>Phrenic long\u2010term facilitation (pLTF) is a serotonin (5\u2010HT)\u2010dependent augmentation of phrenic motor output induced by acute intermittent hypoxia (AIH). AIH\u2010induced pLTF requires spinal NADPH oxidase activity and reactive oxygen species (ROS) formation. Since 5\u2010HT receptor activation stimulates NADPH oxidase activity in some cell types, we tested the hypothesis that episodic spinal 5\u2010HT receptor activation (without AIH) is <jats:italic>sufficient<\/jats:italic> to elicit an NADPH oxidase\u2010dependent facilitation of phrenic motor output (pMF). In anaesthetised, artificially ventilated adult male rats, episodic intrathecal 5\u2010HT injections (3 \u00d7 6 \u03bcl injections at 5 min intervals) into the cerebrospinal fluid (CSF) near cervical spinal segments containing the phrenic motor nucleus elicited a progressive increase in integrated phrenic nerve burst amplitude (i.e. pMF) lasting at least 60 min post\u20105\u2010HT administration. Hypoglossal (XII) nerve activity was unaffected, suggesting that effective doses of 5\u2010HT did not reach the brainstem. A single 5\u2010HT injection was without effect. 5\u2010HT\u2010induced pMF was dose dependent, but exhibited a bell\u2010shaped dose\u2013response curve. Activation of different 5\u2010HT receptor subtypes, specifically 5\u2010HT<jats:sub>2<\/jats:sub><jats:italic>versus<\/jats:italic> 5\u2010HT<jats:sub>7<\/jats:sub> receptors, may underlie the bell\u2010shaped dose\u2013response curve via a mechanism of \u2018cross\u2010talk\u2019 inhibition. Pre\u2010treatment with NADPH oxidase inhibitors, apocynin or diphenylenodium (DPI), blocked 5\u2010HT induced pMF. Thus, episodic spinal 5\u2010HT receptor activation is <jats:italic>sufficient<\/jats:italic> to elicit pMF by an NADPH oxidase\u2010dependent mechanism, suggesting common mechanisms of ROS formation with AIH\u2010induced pLTF. An understanding of the mechanisms giving rise to AIH\u2010induced pLTF and 5\u2010HT induced pMF may inspire novel therapeutic strategies for respiratory insufficiency in diverse conditions, such as sleep apnoea, cervical spinal injury or amyotrophic lateral sclerosis.<\/jats:p>","DOI":"10.1113\/jphysiol.2009.176982","type":"journal-article","created":{"date-parts":[[2009,10,6]],"date-time":"2009-10-06T01:44:46Z","timestamp":1254793486000},"page":"5469-5481","source":"Crossref","is-referenced-by-count":92,"title":["Episodic spinal serotonin receptor activation elicits long\u2010lasting phrenic motor facilitation by an NADPH oxidase\u2010dependent mechanism"],"prefix":"10.1113","volume":"587","author":[{"given":"P. M.","family":"MacFarlane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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