ArticleAmerican journal of physiology. Cell physiology2003
HCO(3)(-)-dependent soluble adenylyl cyclase activates cystic fibrosis transmembrane conductance regulator in corneal endothelium.
Article in American journal of physiology. Cell physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Pathophysiology of cystic fibrosis-related liver disease.Current opinion in gastroenterology · 2026Review
- Review
- Carbonic Anhydrase Inhibitor Modulation of Intraocular Pressure Is Independent of Soluble Adenylyl Cyclase.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
- Carbonic anhydrase and soluble adenylate cyclase regulation of cystic fibrosis cellular phenotypes.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility.Pflugers Archiv : European journal of physiology · 2020Article
- Soluble adenylyl cyclase in health and disease.Biochimica et biophysica acta · 2014Review
- Soluble adenylyl cyclase in the eye.Biochimica et biophysica acta · 2014Review
- Adenylyl cyclases in the digestive system.Cellular signalling · 2014Review
- Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation.Frontiers in physiology · 2014Review
- Lactate-H⁺ transport is a significant component of the in vivo corneal endothelial pump.Investigative ophthalmology & visual science · 2012Article
- Molecular mechanisms underlying the corneal endothelial pump.Experimental eye research · 2012Review
- Regulation of anterior chamber drainage by bicarbonate-sensitive soluble adenylyl cyclase in the ciliary body.The Journal of biological chemistry · 2011Article
- Intracellular cAMP signaling by soluble adenylyl cyclase.Kidney international · 2011Review
- Establishment of a continuous untransfected human corneal endothelial cell line and its biocompatibility to denuded amniotic membrane.Molecular vision · 2011Article
- Soluble adenylyl cyclase mediates bicarbonate-dependent corneal endothelial cell protection.American journal of physiology. Cell physiology · 2011Article
- Physiological carbon dioxide, bicarbonate, and pH sensing.Pflugers Archiv : European journal of physiology · 2010Review
- Decreased soluble adenylyl cyclase activity in cystic fibrosis is related to defective apical bicarbonate exchange and affects ciliary beat frequency regulation.The Journal of biological chemistry · 2010Article
- Somatic 'soluble' adenylyl cyclase isoforms are unaffected in Sacy tm1Lex/Sacy tm1Lex 'knockout' mice.PloS one · 2008Article
- Molecular and functional expression of anion exchangers in cultured normal human nasal epithelial cells.Acta physiologica (Oxford, England) · 2007Article
- Soluble adenylyl cyclase is localized to cilia and contributes to ciliary beat frequency regulation via production of cAMP.The Journal of general physiology · 2007Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
cAMP-dependent activation of the cystic fibrosis transmembrane conductance regulator (CFTR) regulates fluid transport in many tissues. Secretion by the corneal endothelium is stimulated by cAMP and dependent on HCO(3)(-). We asked whether HCO(3)(-) can secondarily increase CFTR permeability in bovine corneal endothelial cells (BCEC) by activating soluble adenylyl cyclase (sAC). Immunofluorescence suggests that sAC is distributed throughout the cytoplasm. HCO(3)(-) (40 mM) increased cAMP concentration 42% in the presence of 50 microM rolipram (a phosphodiesterase 4 inhibitor), and a standard HCO(3)(-) Ringer solution (28.5 mM) increased apical Cl(-) permeability by 78% relative to HCO(3)(-)-free solution. The HCO(3)(-)-dependent increase in Cl(-) permeability was reduced 60% by 20 mM NaHSO(3) (a weak agonist of sAC). NaHSO(3) alone increased apical Cl(-) permeability by only 13%. The HCO(3)(-)-dependent increase in Cl(-) permeability was reduced 57% in the presence of 50 microM Rp-adenosine 3',5'-cyclic monophosphorothioate, and 86% by 50 microM 5-nitro-2-(3-phenylpropyl-amino)benzoic acid but unaffected by 200 microM apical H(2)DIDS. CFTR phosphorylation was increased 23, 150, and 32% by 20 mM HSO(3)(-), 28.5 mM HCO(3)(-), and 28.5 mM HCO(3)(-) + 20 mM HSO(3)(-), respectively. Activation of apical Cl(-) permeability by 5 microM genistein was increased synergistically by HCO(3)(-) over that due to genistein and HCO(3)(-) alone. We conclude that HCO(3)(-)-stimulated sAC is a form of autocrine signaling that contributes to baseline cAMP production, thereby affecting baseline CFTR activity in BCEC. This form of autocrine signaling may be important in tissues that express sAC and exhibit robust HCO(3)(-) influx (e.g., ocular ciliary epithelium, choroid plexus, and airway epithelium).
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