{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:08:38Z","timestamp":1776830918536,"version":"3.51.2"},"reference-count":47,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["HL69064"],"award-info":[{"award-number":["HL69064"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007049","name":"Evelyn F. McKnight Brain Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["F30HL126351"],"award-info":[{"award-number":["F30HL126351"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000848","name":"United Negro College Fund Special Programs Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:p> Acute intermittent hypoxia (AIH) elicits phrenic motor plasticity via multiple distinct cellular mechanisms. With moderate AIH, phrenic motor facilitation (pMF) requires G<jats:sub>q<\/jats:sub> protein-coupled serotonin type 2 receptor activation, ERK MAP kinase activity, and new synthesis of brain-derived neurotrophic factor. In contrast, severe AIH elicits pMF by an adenosine-dependent mechanism that requires exchange protein activated by cAMP, Akt, and mammalian target of rapamycin (mTOR) activity, followed by new tyrosine receptor kinase B protein synthesis; this same pathway is also initiated by G<jats:sub>s<\/jats:sub> protein-coupled serotonin 7 receptors (5-HT<jats:sub>7<\/jats:sub>). Because the metabolic sensor AMP-activated protein kinase (AMPK) inhibits mTOR-dependent protein synthesis, and mTOR signaling is necessary for 5-HT<jats:sub>7<\/jats:sub> but not 5-HT<jats:sub>2<\/jats:sub> receptor-induced pMF, we hypothesized that spinal AMPK activity differentially regulates pMF elicited by these distinct receptor subtypes. Serotonin type 2A receptor [5-HT<jats:sub>2A<\/jats:sub>; (\u00b1)-2,5-dimethoxy-4-iodoamphetamine hydrochloride] or 5-HT<jats:sub>7<\/jats:sub> (AS-19) receptor agonists were administered intrathecally at C<jats:sub>4<\/jats:sub> (3 injections, 5-min intervals) while recording integrated phrenic nerve activity in anesthetized, vagotomized, paralyzed, and ventilated rats. Consistent with our hypothesis, spinal AMPK activation with 2-deoxyglucose or metformin blocked 5-HT<jats:sub>7<\/jats:sub>, but not 5-HT<jats:sub>2A<\/jats:sub> receptor-induced pMF; in both cases, pMF inhibition was reversed by spinal administration of the AMPK inhibitor compound C. Thus, AMPK differentially regulates cellular mechanisms of serotonin-induced phrenic motor plasticity. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Spinal AMP-activated protein kinase (AMPK) overactivity, induced by local 2-deoxyglucose or metformin administration, constrains serotonin 7 (5-HT<jats:sub>7<\/jats:sub>) receptor-induced (but not serotonin type 2A receptor-induced) respiratory motor facilitation, indicating that metabolic challenges might regulate specific forms of respiratory motor plasticity. Pharmacological blockade of spinal AMPK activity restores 5-HT<jats:sub>7<\/jats:sub> receptor-induced respiratory motor facilitation in the presence of either 2-deoxyglucose or metformin, showing that AMPK is an important regulator of 5-HT<jats:sub>7<\/jats:sub> receptor-induced respiratory motor plasticity. <\/jats:p>","DOI":"10.1152\/japplphysiol.00546.2019","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T16:43:56Z","timestamp":1579797836000},"page":"523-533","source":"Crossref","is-referenced-by-count":13,"title":["Spinal AMP kinase activity differentially regulates phrenic motor plasticity"],"prefix":"10.1152","volume":"128","author":[{"given":"Raphael Rodrigues","family":"Perim","sequence":"first","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, 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