{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T04:31:20Z","timestamp":1778905880016,"version":"3.51.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>The carotid body (CB) contributes significantly to oxygen sensing. It is unclear, however, whether glutamatergic signaling is involved in the CB response to hypoxia. Previously, we reported that ionotropic glutamate receptors (iGluRs) and multiple glutamate transporters are present in the rat CB. Except for iGluRs, glutamate receptors also include metabotropic glutamate receptors (mGluRs), which are divided into the following groups: Group I (mGluR1\/5); group II (mGluR2\/3); group III (mGluR4\/6\/7\/8). We have studied the expression of group I mGluRs in the rat CB and its physiological function response to acute hypoxia. To further elucidate the states of mGluRs in the CB, this study\u2019s aim was to investigate the expression of group II and III mGluRs and the response of rat CB to acute hypoxia. We used reverse transcription-polymerase chain reaction (RT-PCR) to observed mRNA expression of GRM2\/3\/4\/6\/7\/8 subunits by using immunostaining to show the distribution of mGluR2 and mGluR8. The results revealed that the GRM2\/3\/4\/6\/7\/8 mRNAs were expressed in both rat and human CB. Immunostaining showed that mGluR2 was localized in the type I cells and mGluR8 was localized in type I and type II cells in the rat CB. Moreover, the response of CB to acute hypoxia in rats was recorded by<jats:italic>in vitro<\/jats:italic>carotid sinus nerve (CSN) discharge. Perfusion of group II mGluRs agonist or group III mGluRs agonist (LY379268 or L-SOP) was applied to examine the effect of group II and III mGluRs on rat CB response to acute hypoxia. We found that LY379268 and L-SOP inhibited hypoxia-induced enhancement of CSN activity. Based on the above findings, group II and III mGluRs appear to play an inhibitory role in the carotid chemoreceptor response to acute hypoxia.<\/jats:p>","DOI":"10.3389\/fphys.2022.1008073","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T13:16:03Z","timestamp":1663852563000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression of group II and III mGluRs in the carotid body and its role in the carotid chemoreceptor response to acute hypoxia"],"prefix":"10.3389","volume":"13","author":[{"given":"Chenlu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaohong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baosheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4269","DOI":"10.1113\/jphysiol.2012.237800","article-title":"Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat","volume":"590","author":"Abdala","year":"2012","journal-title":"J. Physiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1124\/mol.107.035170","article-title":"A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis","volume":"72","author":"Benneyworth","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1111\/j.1460-9568.1997.tb01653.x","article-title":"Glutamate metabotropic receptor agonists depress excitatory and inhibitory transmission on rat mesencephalic principal neurons","volume":"9","author":"Bonci","year":"1997","journal-title":"Eur. J. Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1523\/JNEUROSCI.16-06-02044.1996","article-title":"Immunocytochemical localization of group III metabotropic glutamate receptors in the hippocampus with subtype-specific antibodies","volume":"16","author":"Bradley","year":"1996","journal-title":"J. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1046\/j.1471-4159.2000.0750889.x","article-title":"Regulation of neurotransmitter release by metabotropic glutamate receptors","volume":"75","author":"Cartmell","year":"2000","journal-title":"J. Neurochem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1146\/annurev.pharmtox.37.1.205","article-title":"Pharmacology and functions of metabotropic glutamate receptors","volume":"37","author":"Conn","year":"1997","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1152\/jn.2000.83.5.2519","article-title":"Activation of presynaptic group III metabotropic receptors enhances glutamate release in rat entorhinal cortex","volume":"83","author":"Evans","year":"2000","journal-title":"J. Neurophysiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1113\/jphysiol.2003.048298","article-title":"GABA mediates autoreceptor feedback inhibition in the rat carotid body via presynaptic GABAB receptors and TASK-1","volume":"553","author":"Fearon","year":"2003","journal-title":"J. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.resp.2018.08.007","article-title":"Acute oxygen sensing-Role of metabolic specifications in peripheral chemoreceptor cells","volume":"265","author":"Gao","year":"2019","journal-title":"Respir. Physiol. Neurobiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1152\/physrev.1994.74.4.829","article-title":"Carotid body chemoreceptors: From natural stimuli to sensory discharges","volume":"74","author":"Gonzalez","year":"1994","journal-title":"Physiol. Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1152\/physrev.00039.2019","article-title":"Carotid body chemoreceptors: Physiology, pathology, and implications for health and disease","volume":"101","author":"Iturriaga","year":"2021","journal-title":"Physiol. Rev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.brainresrev.2004.05.007","article-title":"Neurotransmission in the carotid body: Transmitters and modulators between glomus cells and petrosal ganglion nerve terminals","volume":"47","author":"Iturriaga","year":"2004","journal-title":"Brain Res. Brain Res. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1111\/j.1440-1681.2009.05213.x","article-title":"Carotid body potentiation induced by intermittent hypoxia: Implications for cardiorespiratory changes induced by sleep apnoea","volume":"36","author":"Iturriaga","year":"2009","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.brainres.2006.08.119","article-title":"Activation of group II metabotropic glutamate receptors reduces directional selectivity in retinal ganglion cells","volume":"1122","author":"Jensen","year":"2006","journal-title":"Brain Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1038\/mp.2016.129","article-title":"mGluR2\/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both presynaptic and postsynaptic actions","volume":"22","author":"Jin","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1113\/expphysiol.2014.078873","article-title":"The human carotid body releases acetylcholine, ATP and cytokines during hypoxia","volume":"99","author":"K\u00e5hlin","year":"2014","journal-title":"Exp. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1113\/jphysiol.1996.sp021395","article-title":"Activation of metabotropic glutamate receptor type 2\/3 suppresses transmission at rat hippocampal mossy fibre synapses","volume":"493","author":"Kamiya","year":"1996","journal-title":"J. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.2337\/diabetes.49.9.1434","article-title":"Evidence that carotid bodies play an important role in glucoregulation in vivo","volume":"49","author":"Koyama","year":"2000","journal-title":"Diabetes"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1073\/pnas.75.5.2507","article-title":"Carotid body chemoreceptor function: Hypothesis based on a new circuit model","volume":"75","author":"Krammer","year":"1978","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B20","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s12931-020-01468-z","article-title":"Functional glutamate transporters are expressed in the carotid chemoreceptor","volume":"21","author":"Li","year":"2020","journal-title":"Respir. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"741214","DOI":"10.3389\/fnins.2021.741214","article-title":"Metabotropic glutamate receptors 1 regulates rat carotid body response to acute hypoxia via presynaptic mechanism","volume":"15","author":"Li","year":"2021","journal-title":"Front. Neurosci."},{"key":"B22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.55782\/ane-2007-1649","article-title":"Vesicular glutamate transporters (VGLUTs): The three musketeers of glutamatergic system","volume":"67","author":"Liguz-Lecznar","year":"2007","journal-title":"Acta Neurobiol. Exp."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1152\/jn.1993.69.3.1000","article-title":"Activation of metabotropic glutamate receptors induces long-term depression of GABAergic inhibition in hippocampus","volume":"69","author":"Liu","year":"1993","journal-title":"J. Neurophysiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1152\/japplphysiol.90626.2008","article-title":"Exposure to cyclic intermittent hypoxia increases expression of functional NMDA receptors in the rat carotid body","volume":"106","author":"Liu","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1152\/jappl.1983.55.6.1893","article-title":"Interaction between norepinephrine and hypoxia on carotid body chemoreception in rabbits","volume":"55","author":"Milsom","year":"1983","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1017\/S146114571400011X","article-title":"Overexpression of Shati\/Nat8l, an N-acetyltransferase, in the nucleus accumbens attenuates the response to methamphetamine via activation of group II mGluRs in mice","volume":"17","author":"Miyamoto","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1126\/science.281.5381.1349","article-title":"Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats","volume":"281","author":"Moghaddam","year":"1998","journal-title":"Science"},{"key":"B28","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s11357-010-9187-z","article-title":"Carotid body function in aged rats: Responses to hypoxia, ischemia, dopamine, and adenosine","volume":"33","author":"Monteiro","year":"2011","journal-title":"Age Dordr. Neth."},{"key":"B29","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/BF00222070","article-title":"Nerve endings in rat carotid body","volume":"157","author":"Morgan","year":"1975","journal-title":"Cell. Tissue Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","article-title":"Metabotropic glutamate receptors: Physiology, pharmacology, and disease","volume":"50","author":"Niswender","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3419","DOI":"10.1113\/jphysiol.2013.269829","article-title":"Synaptic and paracrine mechanisms at carotid body arterial chemoreceptors","volume":"592","author":"Nurse","year":"2014","journal-title":"J. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1161\/CIRCRESAHA.121.319874","article-title":"GLP1R attenuates sympathetic response to high Glucose via carotid body inhibition","volume":"130","author":"Pauza","year":"2022","journal-title":"Circ. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0028-3908(94)00129-g","article-title":"The metabotropic glutamate receptors: Structure and functions","volume":"34","author":"Pin","year":"1995","journal-title":"Neuropharmacology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1002\/ar.23829","article-title":"The carotid sinus nerve-structure, function, and clinical implications","volume":"302","author":"Porzionato","year":"2019","journal-title":"Anat. Rec."},{"key":"B35","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/j.1440-1681.2005.04209.x","article-title":"Cardiovascular alterations by chronic intermittent hypoxia: Importance of carotid body chemoreflexes","volume":"32","author":"Prabhakar","year":"2005","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/j.neuron.2018.05.018","article-title":"Glutamatergic signaling in the central nervous system: Ionotropic and metabotropic receptors in concert","volume":"98","author":"Reiner","year":"2018","journal-title":"Neuron"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1111\/j.1471-4159.2007.05034.x","article-title":"The C-terminus of the metabotropic glutamate receptor 1b regulates dimerization of the receptor","volume":"104","author":"Remelli","year":"2008","journal-title":"J. Neurochem."},{"key":"B38","doi-asserted-by":"publisher","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":"B39","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/385630a0","article-title":"Use-dependent increases in glutamate concentration activate presynaptic metabotropic glutamate receptors","volume":"385","author":"Scanziani","year":"1997","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/s0006-8993(97)01271-7","article-title":"Multiple pathways for regulation of the KCl-induced [3H]-GABA release by metabotropic glutamate receptors, in primary rat cortical cultures","volume":"782","author":"Schaffhauser","year":"1998","journal-title":"Brain Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1161\/HYPERTENSIONAHA.106.076083","article-title":"Arterial chemoreceptors and sympathetic nerve activity: Implications for hypertension and heart failure","volume":"50","author":"Schultz","year":"2007","journal-title":"Hypertension"},{"key":"B42","doi-asserted-by":"publisher","first-page":"7503","DOI":"10.1523\/JNEUROSCI.17-19-07503.1997","article-title":"Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus","volume":"17","author":"Shigemoto","year":"1997","journal-title":"J. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.neuroscience.2021.06.007","article-title":"Relationships and interactions between ionotropic glutamate receptors and nicotinic receptors in the CNS","volume":"468","author":"Stone","year":"2021","journal-title":"Neuroscience"},{"key":"B44","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/0197-0186(95)00130-1","article-title":"Glutamate in the glomus cells of the cat carotid body: Immunocytochemistry and in vitro release","volume":"28","author":"Torrealba","year":"1996","journal-title":"Neurochem. Int."},{"key":"B45","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1139\/y2012-054","article-title":"Autocrine and paracrine actions of ATP in rat carotid body","volume":"90","author":"Tse","year":"2012","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1093\/cercor\/bhr131","article-title":"Activation of group II metabotropic glutamate receptors inhibits glutamatergic transmission in the rat entorhinal cortex via reduction of glutamate release probability","volume":"22","author":"Wang","year":"2012","journal-title":"Cereb. Cortex"},{"key":"B47","doi-asserted-by":"publisher","first-page":"4335","DOI":"10.1113\/jphysiol.2012.236265","article-title":"P2Y2 receptor activation opens pannexin-1 channels in rat carotid body type II cells: Potential role in amplifying the neurotransmitter ATP","volume":"590","author":"Zhang","year":"2012","journal-title":"J. Physiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1007\/s00702-014-1180-8","article-title":"Glutamate as a neurotransmitter in the healthy brain","volume":"121","author":"Zhou","year":"2014","journal-title":"J. Neural Transm."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.1008073\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T11:46:14Z","timestamp":1728042374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.1008073\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":48,"alternative-id":["10.3389\/fphys.2022.1008073"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.1008073","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,22]]},"article-number":"1008073"}}