{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T09:45:13Z","timestamp":1775382313365,"version":"3.50.1"},"reference-count":125,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2011,2,11]],"date-time":"2011-02-11T00:00:00Z","timestamp":1297382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Carbon dioxide (CO2) is produced by living organisms as a byproduct of metabolism. In physiological systems, CO2 is unequivocally linked with bicarbonate (HCO3\u2212) and pH via a ubiquitous family of carbonic anhydrases, and numerous biological processes are dependent upon a mechanism for sensing the level of CO2, HCO3, and\/or pH. The discovery that soluble adenylyl cyclase (sAC) is directly regulated by bicarbonate provided a link between CO2\/HCO3\/pH chemosensing and signaling via the widely used second messenger cyclic AMP. This review summarizes the evidence that bicarbonate-regulated sAC, and additional, subsequently identified bicarbonate-regulate nucleotidyl cyclases, function as evolutionarily conserved CO2\/HCO3\/pH chemosensors in a wide variety of physiological systems.<\/jats:p>","DOI":"10.3390\/s110202112","type":"journal-article","created":{"date-parts":[[2011,2,11]],"date-time":"2011-02-11T11:07:40Z","timestamp":1297422460000},"page":"2112-2128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Physiological Sensing of Carbon Dioxide\/Bicarbonate\/pH via Cyclic Nucleotide Signaling"],"prefix":"10.3390","volume":"11","author":[{"given":"Jochen","family":"Buck","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA"}]},{"given":"Lonny R.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA"}]}],"member":"1968","published-online":{"date-parts":[[2011,2,11]]},"reference":[{"key":"ref_1","unstructured":"Johnson, L.R. (1998). Essential Medical Physiology, Lippincott-Raven. [2nd ed]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1126\/science.289.5479.625","article-title":"Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor","volume":"289","author":"Chen","year":"2000","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev.bi.37.070168.001053","article-title":"Cyclic AMP","volume":"37","author":"Robison","year":"1968","journal-title":"Ann. Rev. Biochem"},{"key":"ref_4","first-page":"186285","article-title":"A toolkit for real-time detection of cAMP: Insights into compartmentalized signaling","volume":"186","author":"Berrera","year":"2008","journal-title":"Handb. Exp. Pharmacol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nmeth1135","article-title":"Live-cell imaging of cAMP dynamics","volume":"5","author":"Willoughby","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1476-5381.2009.00185.x","article-title":"cAMP signal transduction in the heart: Understanding spatial control for the development of novel therapeutic strategies","volume":"158","author":"Zaccolo","year":"2009","journal-title":"Br. J. Pharmacol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1126\/science.271.5248.461","article-title":"Gating by cyclic AMP: Expanded role for an old signaling pathway","volume":"271","author":"Iyengar","year":"1996","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"pe19","DOI":"10.1126\/stke.2312004pe19","article-title":"Discrete intracellular signaling domains of soluble adenylyl cyclase: Camps of cAMP?","volume":"2004","author":"Bundey","year":"2004","journal-title":"Sci. STKE"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1096\/fj.02-0598fje","article-title":"Compartmentalization of bicarbonate-sensitive adenylyl cyclase in distinct signaling microdomains","volume":"17","author":"Zippin","year":"2003","journal-title":"Faseb. J"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1083\/jcb.200311119","article-title":"Bicarbonate-responsive \u201csoluble\u201d adenylyl cyclase defines a nuclear cAMP microdomain","volume":"164","author":"Zippin","year":"2004","journal-title":"J. Cell Biol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1083\/jcb.200605050","article-title":"PGE(1) stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: Role of compartmentalized phosphodiesterases","volume":"175","author":"Terrin","year":"2006","journal-title":"J. Cell Biol"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gervasi, N., Tch\u00c8nio, P., and Preat, T. (2010). PKA dynamics in a drosophila learning center: Coincidence detection by rutabaga adenylyl cyclase and spatial regulation by dunce phosphodiesterase. 65, 516\u2013529.","DOI":"10.1016\/j.neuron.2010.01.014"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tibs.2009.09.007","article-title":"Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown","volume":"35","author":"Houslay","year":"2010","journal-title":"Trends Biochem. Sci"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1161\/01.RES.0000134629.84732.11","article-title":"Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases","volume":"95","author":"Mongillo","year":"2004","journal-title":"Circ. Res"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cmet.2009.01.012","article-title":"Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation","volume":"9","author":"Salazar","year":"2009","journal-title":"Cell Metab"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ceb.2007.02.011","article-title":"A-kinase anchoring proteins take shape","volume":"19","author":"Beene","year":"2007","journal-title":"Curr. Opin. Cell Biol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/iub.168","article-title":"A-kinase anchoring proteins: From protein complexes to physiology and disease","volume":"61","author":"Carnegie","year":"2009","journal-title":"IUBMB Life"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.molcel.2006.07.025","article-title":"Dynamic regulation of cAMP synthesis through anchored PKA-adenylyl cyclase V\/VI complexes","volume":"23","author":"Bauman","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14450","DOI":"10.1074\/jbc.M110.109769","article-title":"AKAP79 interacts with multiple adenylyl cyclase (AC) isoforms and scaffolds AC5 and -6 to alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors","volume":"285","author":"Efendiev","year":"2010","journal-title":"J. Biol. Chem"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13835","DOI":"10.1073\/pnas.0712100105","article-title":"The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain","volume":"105","author":"Piggott","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1093\/emboj\/20.8.1921","article-title":"mAKAP assembles a protein kinase A\/PDE4 phosphodiesterase cAMP signaling module","volume":"20","author":"Dodge","year":"2001","journal-title":"Embo J"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21999","DOI":"10.1074\/jbc.C000911200","article-title":"Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in the centrosomal area","volume":"276","author":"Tasken","year":"2001","journal-title":"J. Biol. Chem"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ceb.2005.01.003","article-title":"Arrestin times for compartmentalised cAMP signalling and phosphodiesterase-4 enzymes","volume":"17","author":"Baillie","year":"2005","journal-title":"Curr. Opin. Cell Biol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1095\/biolreprod.105.043588","article-title":"AKAP3 selectively binds PDE4A isoforms in bovine spermatozoa","volume":"74","author":"Bajpai","year":"2006","journal-title":"Biol. Reprod"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.ejcb.2006.01.005","article-title":"Spatial organisation of AKAP18 and PDE4 isoforms in renal collecting duct principal cells","volume":"85","author":"McSorley","year":"2006","journal-title":"Eur. J. Cell Biol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1038\/sj.emboj.7601113","article-title":"An anchored PKA and PDE4 complex regulates subplasmalemmal cAMP dynamics","volume":"25","author":"Willoughby","year":"2006","journal-title":"Embo J"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5956","DOI":"10.1074\/jbc.M805606200","article-title":"Spatial distribution of protein kinase A activity during cell migration is mediated by A-kinase anchoring protein AKAP Lbc","volume":"284","author":"Vergara","year":"2009","journal-title":"J. Biol. Chem"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1152\/ajpheart.00425.2008","article-title":"Distinct phosphodiesterase-4D variants integrate into protein kinase A-based signaling complexes in cardiac and vascular myocytes","volume":"296","author":"Raymond","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1172\/JCI108088","article-title":"Stimulation of osmotic water flow in toad bladder by prostaglandin E1. Evidence for different compartments of cyclic AMP","volume":"56","author":"Flores","year":"1975","journal-title":"J. Clin. Invest"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10233","DOI":"10.1016\/S0021-9258(17)44447-4","article-title":"Compartments of cyclic AMP and protein kinase in mammalian cardiomyocytes","volume":"258","author":"Buxton","year":"1983","journal-title":"J. Biol. Chem"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16513","DOI":"10.1073\/pnas.0405973101","article-title":"Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments","volume":"101","author":"DiPilato","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1038\/sj.embor.7400290","article-title":"Detecting cAMP-induced Epac activation by fluorescence resonance energy transfer: Epac as a novel cAMP indicator","volume":"5","author":"Ponsioen","year":"2004","journal-title":"Embo Rep"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1042\/BST0331323","article-title":"Imaging the cAMP-dependent signal transduction pathway","volume":"33","author":"Zaccolo","year":"2005","journal-title":"Biochem. Soc. Trans"},{"key":"ref_34","first-page":"15","article-title":"High-resolution measurements of cyclic adenosine monophosphate signals in 3D microdomains","volume":"307","author":"Karpen","year":"2005","journal-title":"Meth. Mol. Biol"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1085\/jgp.116.2.147","article-title":"Cyclic nucleotide-gated channels colocalize with adenylyl cyclase in regions of restricted cAMP diffusion","volume":"116","author":"Rich","year":"2000","journal-title":"J. Gen. Physiol"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1126\/science.293.5527.98","article-title":"A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2","volume":"293","author":"Davare","year":"2001","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1126\/science.1066843","article-title":"Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel","volume":"295","author":"Marx","year":"2002","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1242\/jcs.011692","article-title":"Spectrin-anchored phosphodiesterase 4D4 restricts cAMP from disrupting microtubules and inducing endothelial cell gap formation","volume":"121","author":"Creighton","year":"2008","journal-title":"J. Cell Sci"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1042\/BST0340492","article-title":"Soluble adenylate cyclase reveals the significance of compartmentalized cAMP on endothelial cell barrier function","volume":"34","author":"Sayner","year":"2006","journal-title":"Biochem. Soc. Trans"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1161\/01.RES.0000209516.84815.3e","article-title":"Soluble adenylyl cyclase reveals the significance of cAMP compartmentation on pulmonary microvascular endothelial cell barrier","volume":"98","author":"Sayner","year":"2006","journal-title":"Circ. Res"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1126\/science.1179735","article-title":"Local and long-range reciprocal regulation of cAMP and cGMP in axon\/dendrite formation","volume":"327","author":"Shelly","year":"2010","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/emmm.200900046","article-title":"Modulation of mitochondrial protein phosphorylation by soluble adenylyl cyclase ameliorates cytochrome oxidase defects","volume":"1","author":"Salazar","year":"2009","journal-title":"Embo Mol. Med"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1085\/jgp.200709784","article-title":"Soluble adenylyl cyclase is localized to cilia and contributes to ciliary beat frequency regulation via production of cAMP","volume":"130","author":"Schmid","year":"2007","journal-title":"J. Gen. Physiol"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.devcel.2005.06.007","article-title":"The \u201csoluble\u201d adenylyl cyclase in sperm mediates multiple signaling events required for fertilization","volume":"9","author":"Hess","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ydbio.2006.05.038","article-title":"Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization","volume":"296","author":"Xie","year":"2006","journal-title":"Dev. Biol"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ydbio.2007.09.017","article-title":"External Ca2+ acts upstream of adenylyl cyclase SACY in the bicarbonate signaled activation of sperm motility","volume":"312","author":"Carlson","year":"2007","journal-title":"Dev. Biol"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1073\/pnas.0400050101","article-title":"Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect","volume":"101","author":"Esposito","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1126\/science.8122111","article-title":"Suppression of Ras-induced transformation of NIH 3T3 cells by activated G alphas","volume":"263","author":"Chen","year":"1994","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0092-8674(95)90398-4","article-title":"Long-range sclerotome induction by sonic hedgehog: Direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway","volume":"81","author":"Fan","year":"1995","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/0092-8674(95)90510-3","article-title":"Protein kinase A and hedgehog signaling in Drosophila limb development","volume":"80","author":"Jiang","year":"1995","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/0092-8674(95)90509-X","article-title":"Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development","volume":"80","author":"Li","year":"1995","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/0896-6273(95)90018-7","article-title":"Postsynaptic cAMP pathway gates early LTP in hippocampal CA1 region","volume":"15","author":"Blitzer","year":"1995","journal-title":"Neuron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/0896-6273(95)90172-8","article-title":"Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture","volume":"15","author":"Kaplan","year":"1995","journal-title":"Neuron"},{"key":"ref_54","unstructured":"Choi, H.B., Gordon, G.R.J., Zhou, N., Tai, C., Ryu, J.K., McLarnon, J.G., Levin, L.R., Buck, J., and MacVIcar, B.A. Metabolic communication between astrocytes and neurons via bicarbonate responsive soluble adenylyl cyclase, Unpublished work."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1085\/jgp.200810044","article-title":"Glucose and GLP-1 stimulate cAMP production via distinct adenylyl cyclases in INS-1E insulinoma cells","volume":"132","author":"Ramos","year":"2008","journal-title":"J. Gen. Physiol"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17253","DOI":"10.1074\/jbc.M603500200","article-title":"Soluble adenylyl cyclase mediates nerve growth factor-induced activation of Rap1","volume":"281","author":"Stessin","year":"2006","journal-title":"J. Biol. Chem"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1038\/nn1767","article-title":"Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones","volume":"9","author":"Wu","year":"2006","journal-title":"Nat. Neurosci"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1007\/s00424-010-0865-6","article-title":"Physiological carbon dioxide, bicarbonate, and pH sensing","volume":"460","author":"Tresguerres","year":"2010","journal-title":"Pflugers Arch"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1073\/pnas.96.1.79","article-title":"Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals","volume":"96","author":"Buck","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.jmb.2006.07.045","article-title":"Molecular details of cAMP generation in Mammalian cells: A tale of two systems","volume":"362","author":"Kamenetsky","year":"2006","journal-title":"J. Mol. Biol"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1152\/ajpcell.00584.2004","article-title":"Cloning and characterization of the human soluble adenylyl cyclase","volume":"288","author":"Geng","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"31698","DOI":"10.1074\/jbc.M011698200","article-title":"Identification and functional analysis of splice variants of the germ cell soluble adenylyl cyclase","volume":"276","author":"Jaiswal","year":"2001","journal-title":"J. Biol. Chem"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e3251","DOI":"10.1371\/journal.pone.0003251","article-title":"Somatic \u201csoluble\u201d adenylyl cyclase isoforms are unaffected in Sacy tm1Lex\/Sacy tm1Lex \u201cknockout\u201d mice","volume":"3","author":"Farrell","year":"2008","journal-title":"Plos One"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8980","DOI":"10.1016\/S0021-9258(18)34229-7","article-title":"A requirement of bicarbonate for Ca2+-induced elevations of cyclic AMP in guinea pig spermatozoa","volume":"257","author":"Garbers","year":"1982","journal-title":"J. Biol. Chem"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/0014-5793(87)81036-0","article-title":"Stimulation of partially purified adenylate cyclase from bull sperm by bicarbonate","volume":"218","author":"Garty","year":"1987","journal-title":"FEBS Lett"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9699","DOI":"10.1016\/S0021-9258(17)39295-5","article-title":"Sodium bicarbonate in seminal plasma stimulates the motility of mammalian spermatozoa through direct activation of adenylate cyclase","volume":"260","author":"Okamura","year":"1985","journal-title":"J. Biol. Chem"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0167-4889(90)90246-A","article-title":"Bicarbonate dependence of cAMP accumulation induced by phorbol esters in hamster spermatozoa","volume":"1054","author":"Visconti","year":"1990","journal-title":"Biochim. Biophy. Acta"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10676","DOI":"10.1073\/pnas.1831008100","article-title":"Calcium regulation of the soluble adenylyl cyclase expressed in mammalian spermatozoa","volume":"100","author":"Jaiswal","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"15922","DOI":"10.1074\/jbc.M212475200","article-title":"Kinetic properties of \u201csoluble\u201d adenylyl cyclase. Synergism between calcium and bicarbonate","volume":"278","author":"Litvin","year":"2003","journal-title":"J. Biol. Chem"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nsmb880","article-title":"Bicarbonate activation of adenylyl cyclase via promotion of catalytic active site closure and metal recruitment","volume":"12","author":"Steegborn","year":"2005","journal-title":"Nat. Struct. Mol. Biol"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1126\/science.278.5345.1907","article-title":"Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTP gamma S","volume":"278","author":"Tesmer","year":"1997","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/S0898-6568(03)00130-X","article-title":"The class III adenylyl cyclases: Multi-purpose signalling modules","volume":"15","author":"Linder","year":"2003","journal-title":"Cell. Signal"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"35033","DOI":"10.1074\/jbc.M303025200","article-title":"A defined subset of adenylyl cyclases is regulated by bicarbonate ion","volume":"278","author":"Cann","year":"2003","journal-title":"J. Biol. Chem"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s00427-004-0432-2","article-title":"Conservation of functional domain structure in bicarbonate-regulated \u201csoluble\u201d adenylyl cyclases in bacteria and eukaryotes","volume":"214","author":"Kobayashi","year":"2004","journal-title":"Dev. Genes Evol"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"R62","DOI":"10.1152\/ajpregu.00761.2009","article-title":"Modulation of NaCl absorption by [HCO3\u2013] in the marine teleost intestine is mediated by soluble adenylyl cyclase","volume":"299","author":"Tresguerres","year":"2010","journal-title":"Amer. J. Physiol.-Regul. Integr. C"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1073\/pnas.0911790107","article-title":"Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid\/base homeostasis","volume":"107","author":"Tresguerres","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1016\/j.cub.2005.10.040","article-title":"Fungal adenylyl cyclase integrates CO(2) sensing with cAMP signaling and virulence","volume":"15","author":"Klengel","year":"2005","journal-title":"Curr. Biol"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1128\/EC.5.1.103-111.2006","article-title":"Cryptococcus neoformans senses CO2 through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1","volume":"5","author":"Mogensen","year":"2006","journal-title":"Eukaryot. Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e1001193","DOI":"10.1371\/journal.ppat.1001193","article-title":"CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans","volume":"6","author":"Hall","year":"2010","journal-title":"Plos Pathog"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1042\/BJ20100617","article-title":"Guanylate cyclase-G, expressed in the Grueneberg ganglion olfactory subsystem, is activated by bicarbonate","volume":"432","author":"Chao","year":"2010","journal-title":"Biochem. J"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.bbrc.2009.12.068","article-title":"Distinct ONE-GC transduction modes and motifs of the odorants: Uroguanylin and CO(2)","volume":"391","author":"Duda","year":"2010","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1021\/bi900441v","article-title":"Stimulation of guanylyl cyclase-D by bicarbonate","volume":"48","author":"Guo","year":"2009","journal-title":"Biochemistry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1073\/pnas.0812220106","article-title":"Guanylyl cyclase-D in the olfactory CO2 neurons is activated by bicarbonate","volume":"106","author":"Sun","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","unstructured":"Tresguerres, M., Levin, L.R., and Buck, J. Intracellular cAMP signaling by soluble adenylyl cyclase. Kidney Int, in press."},{"key":"ref_85","unstructured":"Knobil, E., and Neill, J.D. (1994). The Physiology of Reproduction, Raven Press, Ltd."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1095\/biolreprod44.5.806","article-title":"Bicarbonate: Carbon-dioxide regulation of sperm capacitation, hyperactivated motility, and acrosome reactions","volume":"44","author":"Boatman","year":"1991","journal-title":"Biol. Reprod"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1095\/biolreprod34.2.349","article-title":"Bicarbonate is essential for ferilization of mouse eggs: Mouse sperm require it to undergo the acrosome reaction","volume":"34","author":"Lee","year":"1986","journal-title":"Biol. Reprod"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/mrd.1120180204","article-title":"A computer-assisted assay for mouse sperm hyperactivation demonstrates that bicarbonate but not bovine serum albumin is required","volume":"18","author":"Neill","year":"1987","journal-title":"Gamete Res"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/j.1939-4640.1998.tb01994.x","article-title":"The molecular basis of sperm capacitation","volume":"19","author":"Visconti","year":"1998","journal-title":"J. Androl"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1095\/biolreprod28.1.75","article-title":"Cyclic adenosine 3\u2032,5\u2032 monophosphate, calcium and protein phosphorylation in flagellar motility","volume":"28","author":"Tash","year":"1983","journal-title":"Biol. Reprod"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1242\/dev.121.4.1139","article-title":"Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway","volume":"121","author":"Visconti","year":"1995","journal-title":"Development"},{"key":"ref_92","first-page":"9","article-title":"Cyclic nucleotides and mammalian sperm capacitation","volume":"42","author":"Fraser","year":"1990","journal-title":"J. Reprod. Fertil. Suppl"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/(SICI)1098-2795(200005)56:1<6::AID-MRD2>3.0.CO;2-M","article-title":"Specific expression of soluble adenylyl cyclase in male germ cells","volume":"56","author":"Sinclair","year":"2000","journal-title":"Mol. Reprod. Dev"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/mrd.20409","article-title":"Autoinhibitory regulation of soluble adenylyl cyclase","volume":"73","author":"Chaloupka","year":"2006","journal-title":"Mol. Reprod. Dev"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"9325","DOI":"10.1073\/pnas.0611296104","article-title":"A sperm-specific Na+\/H+ exchanger (sNHE) is critical for expression and in vivo bicarbonate regulation of the soluble adenylyl cyclase (sAC)","volume":"104","author":"Wang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ydbio.2003.09.020","article-title":"Expression of the soluble adenylyl cyclase during rat spermatogenesis: Evidence for cytoplasmic sites of cAMP production in germ cells","volume":"265","author":"Xie","year":"2004","journal-title":"Dev. Biol"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1095\/biolreprod.105.047837","article-title":"Signaling pathways for modulation of mouse sperm motility by adenosine and catecholamine agonists","volume":"74","author":"Schuh","year":"2006","journal-title":"Biol. Reprod"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1113\/jphysiol.1971.sp009400","article-title":"Micropuncture studies of the electrochemical aspects of fluid and electrolyte transport in individual seminiferous tubules, the epididymis, and the vas deferens in rats","volume":"213","author":"Levine","year":"1971","journal-title":"J. Physiol"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"49523","DOI":"10.1074\/jbc.M309543200","article-title":"Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling","volume":"278","author":"Beaulieu","year":"2003","journal-title":"J. Biol. Chem"},{"key":"ref_100","first-page":"2012","article-title":"V-H+-ATPase translocation during blood alkalosis in dogfish gills: Interaction with carbonic anhydrase and involvement in the postfeeding alkaline tide","volume":"292","author":"Tresguerres","year":"2007","journal-title":"Am. J. Physiol"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1242\/jeb.01382","article-title":"Regulation of branchial V-H(+)-ATPase, Na(+)\/K(+)-ATPase and NHE2 in response to acid and base infusions in the Pacific spiny dogfish (Squalus acanthias)","volume":"208","author":"Tresguerres","year":"2005","journal-title":"J. Exp. Biol"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1242\/jeb.02059","article-title":"Microtubule-dependent relocation of branchial V-H+-ATPase to the basolateral membrane in the Pacific spiny dogfish (Squalus acanthias): A role in base secretion","volume":"209","author":"Tresguerres","year":"2006","journal-title":"J. Exp. Biol"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1152\/ajprenal.00406.2007","article-title":"Association of soluble adenylyl cyclase with the V-ATPase in renal epithelial cells","volume":"294","author":"Paunescu","year":"2008","journal-title":"Am. J. Physiol. Renal Physiol"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1152\/ajprenal.00584.2009","article-title":"cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells","volume":"298","author":"Paunescu","year":"2010","journal-title":"Am. J. Physiol. Renal Physiol"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1242\/jeb.028803","article-title":"Regulation of the V-ATPase in kidney epithelial cells: Dual role in acid-base homeostasis and vesicle trafficking","volume":"212","author":"Brown","year":"2009","journal-title":"J. Exp. Biol"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.otc.2010.02.007","article-title":"Cilia dysfunction","volume":"43","author":"Gudis","year":"2010","journal-title":"Otolaryngol. Clin. North Am"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"14760","DOI":"10.1074\/jbc.M900925200","article-title":"Soluble adenylyl cyclase controls mitochondria-dependent apoptosis in coronary endothelial cells","volume":"284","author":"Kumar","year":"2009","journal-title":"J. Biol. Chem"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/ajprenal.00340.2006","article-title":"New insights into the regulation of V-ATPase-dependent proton secretion","volume":"292","author":"Breton","year":"2007","journal-title":"Am. J. Physiol. Renal Physiol"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/jcp.21767","article-title":"Inhibition of osteoclast formation and function by bicarbonate: Role of soluble adenylyl cyclase","volume":"220","author":"Geng","year":"2009","journal-title":"J. Cell. Physiol"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1210\/jcem.87.4.8300","article-title":"Identification and characterization of a gene with base substitutions associated with the absorptive hypercalciuria phenotype and low spinal bone density","volume":"87","author":"Reed","year":"2002","journal-title":"J. Clin. Endocrinol. Metab"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00223-008-9200-z","article-title":"Association of adenylate cyclase 10 (ADCY10) polymorphisms and bone mineral density in healthy adults","volume":"84","author":"Ichikawa","year":"2009","journal-title":"Calcif. Tissue Int"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/02713688208997688","article-title":"Sodium and chloride transport across the isolated rabbit ciliary body","volume":"2","author":"Kishida","year":"1982","journal-title":"Curr. Eye Res"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1152\/ajplegacy.1972.222.4.885","article-title":"Bicarbonate formation in cerebrospinal fluid: Role in sodium transport and pH regulation","volume":"222","author":"Maren","year":"1972","journal-title":"Am. J. Physiol"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1146\/annurev.ph.50.030188.003403","article-title":"The kinetics of HCO3\u2212 synthesis related to fluid secretion, pH control, and CO2 elimination","volume":"50","author":"Maren","year":"1988","journal-title":"Annu. Rev. Physiol"},{"key":"ref_115","first-page":"1060","article-title":"Bicarbonate-activated adenylyl cyclase in fluid-transporting tissues","volume":"264","author":"Mittag","year":"1993","journal-title":"Am. J. Physiol"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1152\/jn.2002.88.2.604","article-title":"CO(2) and pH independently modulate L-type Ca(2+) current in rabbit carotid body glomus cells","volume":"88","author":"Summers","year":"2002","journal-title":"J. Neurophysiol"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0301-0082(98)00009-4","article-title":"Cyclic nucleotide crosstalk and the regulation of cerebral vasodilation","volume":"56","author":"Pelligrino","year":"1998","journal-title":"Prog. Neurobiol"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"8044","DOI":"10.1073\/pnas.0707607105","article-title":"A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans","volume":"105","author":"Bretscher","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"8038","DOI":"10.1073\/pnas.0707469105","article-title":"Acute carbon dioxide avoidance in Caenorhabditis elegans","volume":"105","author":"Hallem","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1073\/pnas.1017354108","article-title":"Receptor-type guanylate cyclase is required for carbon dioxide sensation by Caenorhabditis elegans","volume":"108","author":"Hallem","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature02714","article-title":"Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue","volume":"430","author":"Gray","year":"2004","journal-title":"Nature"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/nature05466","article-title":"Two chemosensory receptors together mediate carbon dioxide detection in Drosophila","volume":"445","author":"Jones","year":"2007","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/nrn2789","article-title":"Olfactory signalling in vertebrates and insects: Differences and commonalities","volume":"11","author":"Kaupp","year":"2010","journal-title":"Nat. Rev. Neurosci"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1126\/science.1144233","article-title":"Detection of near-atmospheric concentrations of CO2 by an olfactory subsystem in the mouse","volume":"317","author":"Hu","year":"2007","journal-title":"Science"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neuron.2010.12.018","article-title":"Out of thin air: Sensory detection of oxygen and carbon dioxide","volume":"69","author":"Scott","year":"2011","journal-title":"Neuron"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/11\/2\/2112\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:55:12Z","timestamp":1760219712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/11\/2\/2112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,11]]},"references-count":125,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2011,2]]}},"alternative-id":["s110202112"],"URL":"https:\/\/doi.org\/10.3390\/s110202112","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,11]]}}}