{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:53:43Z","timestamp":1790132023598,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2017,7,9]],"date-time":"2017-07-09T00:00:00Z","timestamp":1499558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000855","name":"University of Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Carotid body dysfunction is recognized as a cause of hypertension in a number of cardiorespiratory diseases states and has therefore been identified as a potential therapeutic target.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Purinergic transmission is an important element of the carotid body chemotransduction pathway.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We show that inhibition of ecto\u20105\u2032\u2010nucleotidase (CD73)<jats:italic>in vitro<\/jats:italic>reduces carotid body basal discharge and responses to hypoxia and mitochondrial inhibition.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Additionally, inhibition of CD73<jats:italic>in vivo<\/jats:italic>decreased the hypoxic ventilatory response, reduced the hypoxia\u2010induced heart rate elevation and exaggerated the blood pressure decrease in response to hypoxia.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Our data show CD73 to be a novel regulator of carotid body sensory function and therefore suggest that this enzyme may offer a new target for reducing carotid body activity in selected cardiovascular diseases.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Augmented sensory neuronal activity from the carotid body (CB) has emerged as a principal cause of hypertension in a number of cardiovascular related pathologies, including obstructive sleep apnoea, heart failure and diabetes. Development of new targets and pharmacological treatment strategies aiming to reduce CB sensory activity may thus improve outcomes in these key patient cohorts. The present study investigated whether ecto\u20105\u2032\u2010nucleotidase (CD73), an enzyme that generates adenosine, is functionally important in modifying CB sensory activity and cardiovascular respiratory responses to hypoxia. Inhibition of CD73 by \u03b1,\u03b2\u2010methylene ADP (AOPCP) in the whole CB preparation<jats:italic>in vitro<\/jats:italic>reduced basal discharge frequency by 76\u00a0\u00b1\u00a05% and reduced sensory activity throughout graded hypoxia. AOPCP also significantly attenuated elevations in sensory activity evoked by mitochondrial inhibition. These effects were mimicked by antagonism of adenosine receptors with 8\u2010(<jats:italic>p<\/jats:italic>\u2010sulfophenyl) theophylline. Infusion of AOPCP<jats:italic>in vivo<\/jats:italic>significantly decreased the hypoxic ventilatory response (\u0394<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12454-math-0001.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12454:tjp12454-math-0001\"\/><jats:sub>E<\/jats:sub>control 74\u00a0\u00b1\u00a06%, \u0394<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12454-math-0002.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12454:tjp12454-math-0002\"\/><jats:sub>E<\/jats:sub>AOPCP 64\u00a0\u00b1\u00a05%,<jats:italic>P\u00a0&lt;\u00a0<\/jats:italic>0.05). AOPCP also modified cardiovascular responses to hypoxia, as indicated by reduced elevations in heart rate and exaggerated changes in femoral vascular conductance and mean arterial blood pressure. Thus we identify CD73 as a novel regulator of CB sensory activity. Future investigations are warranted to clarify whether inhibition of CD73 can effectively reduce CB activity in CB\u2010mediated cardiovascular pathology.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp274498","type":"journal-article","created":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T05:22:47Z","timestamp":1496208167000},"page":"3137-3148","source":"Crossref","is-referenced-by-count":19,"title":["Ecto\u20105\u2032\u2010nucleotidase (CD73) regulates peripheral chemoreceptor activity and cardiorespiratory responses to hypoxia"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-9401","authenticated-orcid":false,"given":"Andrew P.","family":"Holmes","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-1013","authenticated-orcid":false,"given":"Clare J.","family":"Ray","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences University of Birmingham Edgbaston Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5243-1097","authenticated-orcid":false,"given":"Selina A.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Mouse Pipelines, Wellcome Trust Sanger Institute Wellcome Genome Campus Hinxton Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9451-4704","authenticated-orcid":false,"given":"Andrew M.","family":"Coney","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences University of Birmingham Edgbaston Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7524-6046","authenticated-orcid":false,"given":"Prem","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences University of Birmingham Edgbaston Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5817-12.2013"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R300032200"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.257741"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1139\/o98-095","article-title":"Recent advances in the molecular biology of nucleoside transporters of mammalian cells","volume":"76","author":"Cass CE","year":"1998","journal-title":"Biochem Cell Biol"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-014-9421-8"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05704.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02380.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01617.2011"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03912.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07255"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019115"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01777-1"},{"key":"e_1_2_6_14_1","first-page":"549","article-title":"Expression and localization of A2a and A1\u2010adenosine receptor genes in the rat carotid body and petrosal ganglia. 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