{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:57:41Z","timestamp":1767981461964,"version":"3.49.0"},"reference-count":64,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2009,8,14]],"date-time":"2009-08-14T00:00:00Z","timestamp":1250208000000},"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":[[2009,8,15]]},"abstract":"<jats:p>Chemoreceptor cells of the carotid bodies (CB) are activated by hypoxia and acidosis, responding with an increase in their rate of neurotransmitter release, which in turn increases the electrical activity in the carotid sinus nerve and evokes a homeostatic hyperventilation. Studies in isolated chemoreceptor cells have shown that moderate hypoxias (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_3594_mu2.gif\" xlink:title=\"inline image\"\/>\u2248 46 mmHg) produces smaller depolarisations and comparable Ca<jats:sup>2+<\/jats:sup> transients but a much higher catecholamine (CA) release response in intact CBs than intense acidic\/hypercapnic stimuli (20% CO<jats:sub>2<\/jats:sub>, pH 6.6). Similarly, intense hypoxia (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_3594_mu3.gif\" xlink:title=\"inline image\"\/>\u2248 20 mmHg) produces smaller depolarizations and Ca<jats:sup>2+<\/jats:sup> transients in isolated chemoreceptor cells but a higher CA release response in intact CBs than a pure depolarizing stimulus (30\u201335 m<jats:sc>m<\/jats:sc> external K<jats:sup>+<\/jats:sup>). Studying the mechanisms responsible for these differences we have found the following. (1) Acidic hypercapnia inhibited <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> (\u223c60%; whole cell) and CA release (\u223c45%; intact CB) elicited by ionomycin and high K<jats:sup>+<\/jats:sup>. (2) Adenylate cyclase inhibition (SQ\u201022536; 80 \u03bc<jats:sc>m<\/jats:sc>) inhibited the hypoxic release response (&gt;50%) and did not affect acidic\/hypercapnic release, evidencing that the high gain of hypoxia to elicit neurotransmitter release is cAMP dependent. (3) The last effect was independent of PKA activation, as three kinase inhibitors (H\u201089, KT 5720 and Rp\u2010cAMP; \u2265 10 \u00d7 IC<jats:sub>50<\/jats:sub>) did not alter the hypoxic release response. (4) The Epac (exchange protein activated by cAMP) activator (8\u2010pCPT\u20102\u2032\u2010<jats:italic>O<\/jats:italic>\u2010Me\u2010cAMP, 100 \u03bc<jats:sc>m<\/jats:sc>) reversed the effects of the cyclase inhibitor. (5) The Epac inhibitor brefeldin A (100 \u03bc<jats:sc>m<\/jats:sc>) inhibited (54%) hypoxic induced release. Our findings show for the first time that an Epac\u2010mediated pathway mediates O<jats:sub>2<\/jats:sub> sensing\/transduction in chemoreceptor cells.<\/jats:p>","DOI":"10.1113\/jphysiol.2009.172072","type":"journal-article","created":{"date-parts":[[2009,7,7]],"date-time":"2009-07-07T01:07:17Z","timestamp":1246928837000},"page":"4015-4027","source":"Crossref","is-referenced-by-count":26,"title":["EPAC signalling pathways are involved in low <i>P<\/i><sub>O2<\/sub> chemoreception in carotid body chemoreceptor cells"],"prefix":"10.1113","volume":"587","author":[{"given":"Asuncion","family":"Rocher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana I.","family":"Caceres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Almaraz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constancio","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,8,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00127-9"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.058818"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-22-08323.2000"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1986.sp016254"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(79)90083-5"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(96)76594-3"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1975.sp010950"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020239"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020143"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01195.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019651"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.497bg.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016687"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.108.5.363"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-31311-7_33"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-2259-2_17"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00459.2001"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.279.1.L36"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00498553"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1982.sp014439"},{"key":"e_1_2_5_22_1","first-page":"247","volume-title":"Handbook of Physiology, section 3, The Respiratory System, vol II, Control of Breathing","author":"Fidone S","year":"1986"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1982.sp014441"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(71)90054-5"},{"key":"e_1_2_5_25_1","first-page":"27","volume-title":"Morphology and Mechanisms of Chemoreceptors","author":"Fitzgerald RS","year":"1976"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(92)90357-E"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1994.74.4.829"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.119644"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.2170\/jjphysiol.35.535"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.018093"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1999.81.4.1839"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.103.4.665"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.66.3.622"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.91.5.641"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(95)90194-9"},{"key":"e_1_2_5_36_1","first-page":"138","volume-title":"Morphology and Mechanisms of Chemoreceptors","author":"Lahiri S","year":"1976"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(75)90017-1"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019456"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00023.x"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.107.1.133"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00008-8"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(86)90806-1"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90260-9"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020749"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb03137.x"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1991.tb06414.x"},{"key":"e_1_2_5_47_1","first-page":"79","volume-title":"The Carotid Body Chemoreceptors","author":"Perez\u2010Garc\u00eda MT","year":"1997"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-15-05689.2000"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.105bl.x"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(84)91026-6"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(86)90398-7"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018441"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.075523"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.018382"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0209k.x"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2005"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.157461"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.26.041002.131412"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.101.5.695"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.96.5.973"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1976.tb04431.x"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.1.C51"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.278.3.C490"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.03.003"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.599bg.x"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2009.172072","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2009.172072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T18:58:18Z","timestamp":1697050698000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2009.172072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,14]]},"references-count":64,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2009,8,15]]}},"alternative-id":["10.1113\/jphysiol.2009.172072"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2009.172072","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,14]]}}}