{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:34:42Z","timestamp":1788222882173,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,3,11]],"date-time":"2018-03-11T00:00:00Z","timestamp":1520726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL069064"],"award-info":[{"award-number":["HL069064"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL119606"],"award-info":[{"award-number":["HL119606"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,4,15]]},"abstract":"\n Key points<\/jats:title>\n \n \n \n \n Although adenosine 2A (A\n 2A<\/jats:sub>\n ) receptor activation triggers specific cell signalling cascades, the ensuing physiological outcomes depend on the specific cell type expressing these receptors.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Cervical spinal adenosine 2A (A\n 2A<\/jats:sub>\n ) receptor activation elicits a prolonged facilitation in phrenic nerve activity, which was nearly abolished following intrapleural A\n 2A<\/jats:sub>\n receptor siRNA injections.\n <\/jats:p>\n <\/jats:list-item>\n \n \n A\n 2A<\/jats:sub>\n receptor siRNA injections selectively knocked down A\n 2A<\/jats:sub>\n receptors in cholera toxin B\u2010subunit\u2010identified phrenic motor neurons, sparing cervical non\u2010phrenic motor neurons.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Collectively, our results support the hypothesis that phrenic motor neurons express the A\n 2A<\/jats:sub>\n receptors relevant to A\n 2A<\/jats:sub>\n receptor\u2010induced phrenic motor facilitation.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Upregulation of A\n 2A<\/jats:sub>\n receptor expression in the phrenic motor neurons\n per se<\/jats:italic>\n may potentially be a useful approach to increase phrenic motor neuron excitability in conditions such as spinal cord injury.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Abstract<\/jats:title>\n \n Cervical spinal adenosine 2A (A\n 2A<\/jats:sub>\n ) receptor activation elicits a prolonged increase in phrenic nerve activity, an effect known as phrenic motor facilitation (pMF). The specific cervical spinal cells expressing the relevant A\n 2A<\/jats:sub>\n receptors for pMF are unknown. This is an important question since the physiological outcome of A\n 2A<\/jats:sub>\n receptor activation is highly cell type specific. Thus, we tested the hypothesis that the relevant A\n 2A<\/jats:sub>\n receptors for pMF are expressed in phrenic motor neurons\n per se versus<\/jats:italic>\n non\u2010phrenic neurons of the cervical spinal cord. A\n 2A<\/jats:sub>\n receptor immunostaining significantly colocalized with NeuN\u2010positive neurons (89\u00a0\u00b1\u00a02%). Intrapleural siRNA injections were used to selectively knock down A\n 2A<\/jats:sub>\n receptors in cholera toxin B\u2010subunit\u2010labelled phrenic motor neurons. A\n 2A<\/jats:sub>\n receptor knock\u2010down was verified by a \u223c45% decrease in A\n 2A<\/jats:sub>\n receptor immunoreactivity within phrenic motor neurons\n versus<\/jats:italic>\n non\u2010targeting siRNAs (siNT;\n P<\/jats:italic>\n \u00a0<\u00a00.05). There was no evidence for knock\u2010down in cervical non\u2010phrenic motor neurons. In rats that were anaesthetized, subjected to neuromuscular blockade and ventilated, pMF induced by cervical (C3\u20134) intrathecal injections of the A\n 2A<\/jats:sub>\n receptor agonist CGS21680 was greatly attenuated in siA\n 2A<\/jats:sub>\n (21%)\n versus<\/jats:italic>\n siNT treated rats (147%;\n P<\/jats:italic>\n \u00a0<\u00a00.01). There were no significant effects of siA\n 2A<\/jats:sub>\n on phrenic burst frequency. Collectively, our results support the hypothesis that phrenic motor neurons express the A\n 2A<\/jats:sub>\n receptors relevant to A\n 2A<\/jats:sub>\n receptor\u2010induced pMF.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp275462","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T22:22:42Z","timestamp":1517437362000},"page":"1501-1512","source":"Crossref","is-referenced-by-count":40,"title":["Phrenic motor neuron adenosine 2A receptors elicit phrenic motor facilitation"],"prefix":"10.1113","volume":"596","author":[{"given":"Yasin B.","family":"Seven","sequence":"first","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute University of Florida Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael R.","family":"Perim","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute University of Florida Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orinda R.","family":"Hobson","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute University of Florida Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec K.","family":"Simon","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute University of Florida Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash","family":"Tadjalli","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute University of Florida Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8489-1861","authenticated-orcid":false,"given":"Gordon S.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute University of Florida Gainesville FL 32610 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