{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:19:58Z","timestamp":1791101998011,"version":"4.1.0"},"reference-count":77,"publisher":"Society for Neuroscience","issue":"5","license":[{"start":{"date-parts":[[2007,7,31]],"date-time":"2007-07-31T00:00:00Z","timestamp":1185840000000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,1,31]]},"abstract":"<jats:p>\n                    ATP is released during hypoxia from the ventrolateral medulla (VLM) and activates purinergic P2 receptors (P2Rs) at unknown loci to offset the secondary hypoxic depression of breathing. In this study, we used rhythmically active medullary slices from neonatal rat to map, in relation to anatomical and molecular markers of the pre-B\u00f6tzinger complex (preB\u00f6tC) (a proposed site of rhythm generation), the effects of ATP on respiratory rhythm and identify the P2R subtypes responsible for these actions. Unilateral microinjections of ATP in a three-dimensional grid within the VLM revealed a \u201chotspot\u201d where ATP (0.1 m\n                    <jats:sc>m<\/jats:sc>\n                    ) evoked a rapid 2.2 \u00b1 0.1-fold increase in inspiratory frequency followed by a brief reduction to 0.83 \u00b1 0.02 of baseline. The hotspot was identified as the preB\u00f6tC based on histology, overlap of injection sites with NK1R immunolabeling, and potentiation or inhibition of respiratory frequency by SP ([Sar\n                    <jats:sup>9<\/jats:sup>\n                    -Met(O\n                    <jats:sub>2<\/jats:sub>\n                    )\n                    <jats:sup>11<\/jats:sup>\n                    ]-substance P) or DAMGO ([\n                    <jats:sc>d<\/jats:sc>\n                    -Ala\n                    <jats:sup>2<\/jats:sup>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    -MePhe\n                    <jats:sup>4<\/jats:sup>\n                    ,Gly-ol\n                    <jats:sup>5<\/jats:sup>\n                    ]-enkephalin), respectively. The relative potency of P2R agonists [2MeSADP (2-methylthioadenosine 5\u2032-diphosphate) \u2248 2MeSATP (2-methylthioadenosine 5\u2032-triphosphate) \u2248 ATP\u03b3s (adenosine 5\u2032-[\u03b3-thio]triphosphate tetralithium salt) \u2248 ATP \u226b UTP \u2248 \u03b1\u03b2meATP (\u03b1,\u03b2-methylene-adenosine 5\u2032-triphosphate)] and attenuation of the ATP response by MRS2179 (2\u2032-deoxy-\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine-3\u2032,5\u2032-bisphosphate) (P2Y\n                    <jats:sub>1<\/jats:sub>\n                    antagonist) indicate that the excitation is mediated by P2Y\n                    <jats:sub>1<\/jats:sub>\n                    Rs. The post-ATP inhibition, which was never observed in response to ATP\u03b3s, is dependent on ATP hydrolysis. These data establish in neonatal rats that respiratory rhythm generating networks in the preB\u00f6tC are exquisitely sensitive to P2Y\n                    <jats:sub>1<\/jats:sub>\n                    R activation, and suggest a role for P2Y\n                    <jats:sub>1<\/jats:sub>\n                    Rs in respiratory motor control, particularly in the P2R excitation of rhythm that occurs during hypoxia.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.3948-06.2007","type":"journal-article","created":{"date-parts":[[2007,2,2]],"date-time":"2007-02-02T20:16:38Z","timestamp":1170447398000},"page":"993-1005","source":"Crossref","is-referenced-by-count":69,"title":["P2Y\n                    <sub>1<\/sub>\n                    Receptor Modulation of the Pre-B\u00f6tzinger Complex Inspiratory Rhythm Generating Network\n                    <i>In Vitro<\/i>"],"prefix":"10.1523","volume":"27","author":[{"given":"Amanda R.","family":"Lorier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianne G.","family":"Huxtable","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean M.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Lipski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Housley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Funk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,1,31]]},"reference":[{"key":"2023041303231399000_27.5.993.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04261.x"},{"key":"2023041303231399000_27.5.993.2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013192"},{"key":"2023041303231399000_27.5.993.3","doi-asserted-by":"publisher","DOI":"10.1021\/jm970433l"},{"key":"2023041303231399000_27.5.993.4","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1523\/JNEUROSCI.16-08-02495.1996","article-title":"Cloning of P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels","volume":"16","author":"Collo","year":"1996","journal-title":"J Neurosci"},{"key":"2023041303231399000_27.5.993.5","doi-asserted-by":"publisher","DOI":"10.1038\/383259a0"},{"key":"2023041303231399000_27.5.993.6","doi-asserted-by":"crossref","first-page":"7673","DOI":"10.1523\/JNEUROSCI.17-20-07673.1997","article-title":"Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus","volume":"17","author":"Dunwiddie","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303231399000_27.5.993.7","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1871"},{"key":"2023041303231399000_27.5.993.8","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1928"},{"key":"2023041303231399000_27.5.993.9","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1152\/jn.1993.70.4.1497","article-title":"Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids","volume":"70","author":"Funk","year":"1993","journal-title":"J Neurophysiol"},{"key":"2023041303231399000_27.5.993.10","doi-asserted-by":"crossref","first-page":"6325","DOI":"10.1523\/JNEUROSCI.17-16-06325.1997","article-title":"P2 receptor excitation of rodent hypoglossal motoneuron activity in vitro and in vivo: a molecular physiological analysis","volume":"17","author":"Funk","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303231399000_27.5.993.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(97)00078-9"},{"key":"2023041303231399000_27.5.993.12","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.045294"},{"key":"2023041303231399000_27.5.993.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3763-04.2005"},{"key":"2023041303231399000_27.5.993.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature03690"},{"key":"2023041303231399000_27.5.993.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5444.1566"},{"key":"2023041303231399000_27.5.993.16","doi-asserted-by":"publisher","DOI":"10.1038\/nn0901-927"},{"key":"2023041303231399000_27.5.993.17","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1113\/jphysiol.1991.sp018622","article-title":"Role of excitatory amino acids in the generation and transmission of respiratory drive in neonatal rat","volume":"437","author":"Greer","year":"1991","journal-title":"J Physiol (Lond)"},{"key":"2023041303231399000_27.5.993.18","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1152\/jn.2001.86.1.438","article-title":"Pre-Botzinger neurons with preinspiratory discharges \u201cin vivo\u201d express NK1 receptors in the rat","volume":"86","author":"Guyenet","year":"2001","journal-title":"J Neurophysiol"},{"key":"2023041303231399000_27.5.993.19","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.1523\/JNEUROSCI.22-09-03806.2002","article-title":"Neurokinin-1 receptor-expressing cells of the ventral respiratory group are functionally heterogeneous and predominantly glutamatergic","volume":"22","author":"Guyenet","year":"2002","journal-title":"J Neurosci"},{"key":"2023041303231399000_27.5.993.20","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000314"},{"key":"2023041303231399000_27.5.993.21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0159r.x"},{"key":"2023041303231399000_27.5.993.22","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1203\/00006450-199707000-00008","article-title":"Adenosine modulates inspiratory neurons and the respiratory pattern in the brainstem of neonatal rats","volume":"42","author":"Herlenius","year":"1997","journal-title":"Pediatr Res"},{"key":"2023041303231399000_27.5.993.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(00)00048-1"},{"key":"2023041303231399000_27.5.993.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-006-0063-8"},{"key":"2023041303231399000_27.5.993.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2003.10.030"},{"key":"2023041303231399000_27.5.993.26","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1152\/jappl.1996.80.6.2120","article-title":"Modulation of respiratory rhythm in vitro: role of Gi\/o protein-mediated mechanisms","volume":"80","author":"Johnson","year":"1996","journal-title":"J Appl Physiol"},{"key":"2023041303231399000_27.5.993.27","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.4.979"},{"key":"2023041303231399000_27.5.993.28","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990428)407:1<11::AID-CNE2>3.0.CO;2-R"},{"key":"2023041303231399000_27.5.993.29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0469k.x"},{"key":"2023041303231399000_27.5.993.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(00)00171-1"},{"key":"2023041303231399000_27.5.993.31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3028-04.2004"},{"key":"2023041303231399000_27.5.993.32","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1111\/j.1476-5381.1996.tb15293.x","article-title":"Full sensitivity of P2X2 purinoceptor to ATP revealed by changing extracellular pH","volume":"117","author":"King","year":"1996","journal-title":"Br J Pharmacol"},{"key":"2023041303231399000_27.5.993.33","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701286"},{"key":"2023041303231399000_27.5.993.34","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000312"},{"key":"2023041303231399000_27.5.993.35","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1152\/jn.1990.64.2.423","article-title":"Excitatory amino acid-mediated transmission of inspiratory drive to phrenic motoneurons","volume":"64","author":"Liu","year":"1990","journal-title":"J Neurophysiol"},{"key":"2023041303231399000_27.5.993.36","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10111"},{"key":"2023041303231399000_27.5.993.37","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/ppul.1950170109","article-title":"Role of adenosine in the hypoxic ventilatory response of the newborn piglet","volume":"17","author":"Lopes","year":"1994","journal-title":"Pediatr Pulmonol"},{"key":"2023041303231399000_27.5.993.38","first-page":"173.8","article-title":"Modulation of respiratory rhythm generating networks by ATP","volume":"28","author":"Lorier","year":"2002","journal-title":"Soc Neurosci Abstr"},{"key":"2023041303231399000_27.5.993.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2004.04.007"},{"key":"2023041303231399000_27.5.993.40","doi-asserted-by":"publisher","DOI":"10.1038\/nn1517"},{"key":"2023041303231399000_27.5.993.41","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00475.2001"},{"key":"2023041303231399000_27.5.993.42","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1152\/jn.1999.81.1.247","article-title":"A1 adenosine receptors modulate respiratory activity of the neonatal mouse via the cAMP-mediated signaling pathway","volume":"81","author":"Mironov","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041303231399000_27.5.993.43","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1696-06.2006"},{"key":"2023041303231399000_27.5.993.44","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91586-0"},{"key":"2023041303231399000_27.5.993.45","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701386"},{"key":"2023041303231399000_27.5.993.46","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000311"},{"key":"2023041303231399000_27.5.993.47","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2002"},{"key":"2023041303231399000_27.5.993.48","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev.pharmtox.40.1.563","article-title":"Pharmacology of cloned P2X receptors","volume":"40","author":"North","year":"2000","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"2023041303231399000_27.5.993.49","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-006-0060-y"},{"key":"2023041303231399000_27.5.993.50","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(93)90077-N"},{"key":"2023041303231399000_27.5.993.51","doi-asserted-by":"crossref","first-page":"9575","DOI":"10.1523\/JNEUROSCI.23-29-09575.2003","article-title":"Ontogeny of the pre-Botzinger complex in perinatal rats","volume":"23","author":"Pagliardini","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303231399000_27.5.993.52","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4930-04.2005"},{"key":"2023041303231399000_27.5.993.53","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00529-7"},{"key":"2023041303231399000_27.5.993.54","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.012836"},{"key":"2023041303231399000_27.5.993.55","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0031-6997(24)01373-5","article-title":"Receptors for purines and pyrimidines","volume":"50","author":"Ralevic","year":"1998","journal-title":"Pharmacol Rev"},{"key":"2023041303231399000_27.5.993.56","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1152\/jn.1997.78.1.383","article-title":"Developmental changes in the hypoxic response of the hypoglossus respiratory motor output in vitro","volume":"78","author":"Ramirez","year":"1997","journal-title":"J Neurophysiol"},{"key":"2023041303231399000_27.5.993.57","doi-asserted-by":"crossref","first-page":"11315","DOI":"10.1523\/JNEUROSCI.23-36-11315.2003","article-title":"Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia","volume":"23","author":"Rong","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303231399000_27.5.993.58","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1152\/jappl.1989.67.2.541","article-title":"Role of adenosine in hypoxic ventilatory depression","volume":"67","author":"Runold","year":"1989","journal-title":"J Appl Physiol"},{"key":"2023041303231399000_27.5.993.59","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(98)00066-5"},{"key":"2023041303231399000_27.5.993.60","doi-asserted-by":"publisher","DOI":"10.1126\/science.1683005"},{"key":"2023041303231399000_27.5.993.61","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(00)00118-1"},{"key":"2023041303231399000_27.5.993.62","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10504"},{"key":"2023041303231399000_27.5.993.63","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1152\/jn.1999.82.5.2163","article-title":"Differential responses of respiratory nuclei to anoxia in rhythmic brain stem slices of mice","volume":"82","author":"Telgkamp","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041303231399000_27.5.993.64","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00441.x"},{"key":"2023041303231399000_27.5.993.65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00899.x"},{"key":"2023041303231399000_27.5.993.66","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00363-3"},{"key":"2023041303231399000_27.5.993.67","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1113\/jphysiol.1996.sp021720","article-title":"Acidosis of rat dorsal vagal neurons in situ during spontaneous and evoked activity","volume":"496","author":"Trapp","year":"1996","journal-title":"J Physiol (Lond)"},{"key":"2023041303231399000_27.5.993.68","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1113\/jphysiol.1997.sp021946","article-title":"Interstitial PCO2 and pH, and their role as chemostimulants in the isolated respiratory network of neonatal rats","volume":"499","author":"Voipio","year":"1997","journal-title":"J Physiol (Lond)"},{"key":"2023041303231399000_27.5.993.69","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.pharmthera.2005.08.014","article-title":"Pharmacological profiles of cloned mammalian P2Y-receptor subtypes","volume":"110","author":"von Kugelgen","year":"2005","journal-title":"Pharmacol Ther"},{"key":"2023041303231399000_27.5.993.70","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000310"},{"key":"2023041303231399000_27.5.993.71","doi-asserted-by":"publisher","DOI":"10.1002\/cne.1169"},{"key":"2023041303231399000_27.5.993.72","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00952.2003"},{"key":"2023041303231399000_27.5.993.73","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1152\/jn.1999.81.5.2088","article-title":"Differential modulation by copper and zinc of P2X2 and P2X4 receptor function","volume":"81","author":"Xiong","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041303231399000_27.5.993.74","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1152\/jappl.1995.79.2.405","article-title":"Microdialyzed adenosine in nucleus tractus solitarii and ventilatory response to hypoxia in piglets","volume":"79","author":"Yan","year":"1995","journal-title":"J Appl Physiol"},{"key":"2023041303231399000_27.5.993.75","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20001127)427:4<485::AID-CNE1>3.0.CO;2-S"},{"key":"2023041303231399000_27.5.993.76","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000309"},{"key":"2023041303231399000_27.5.993.77","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/ddr.1097","article-title":"Ectonucleotidases: some recent developments and a note on nomenclature","volume":"52","author":"Zimmermann","year":"2001","journal-title":"Drug Dev Res"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.3948-06.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T03:51:40Z","timestamp":1736740300000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.3948-06.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1,31]]},"references-count":77,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2007,1,31]]},"published-print":{"date-parts":[[2007,1,31]]}},"alternative-id":["10.1523\/JNEUROSCI.3948-06.2007"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.3948-06.2007","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,1,31]]}}}