| http://purl.uniprot.org/citations/37154494 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37154494 | http://www.w3.org/2000/01/rdf-schema#comment | "In polarized intestinal epithelial cells, downregulated in adenoma (DRA) is an apical Cl-/[Formula: see text] exchanger that is part of neutral NaCl absorption under baseline conditions, but in cyclic adenosine monophosphate (cAMP)-driven diarrheas, it is stimulated and contributes to increased anion secretion. To further understand the regulation of DRA in conditions mimicking some diarrheal diseases, Caco-2/BBE cells were exposed to forskolin (FSK) and adenosine 5'-triphosphate (ATP). FSK and ATP stimulated DRA in a concentration-dependent manner, with ATP acting via P2Y1 receptors. FSK at 1 µM and ATP at 0.25 µM had minimal to no effect on DRA given individually; however, together, they stimulated DRA to levels seen with maximum concentrations of FSK and ATP alone. In Caco-2/BBE cells expressing the Ca2+ indicator GCaMP6s, ATP increased intracellular Ca2+ (Ca2+i) in a concentration-dependent manner, whereas FSK (1 µM), which by itself did not significantly alter Ca2+i, followed by 0.25 µM ATP produced a large increase in Ca2+ that was approximately equal to the elevation caused by 1 µM ATP. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM) pretreatment prevented the ATP and FSK/ATP synergistically increased the DRA activity and the increase in Ca2+i caused by FSK/ATP. FSK/ATP synergistic stimulation of DRA was similarly observed in human colonoids. In Caco-2/BBE cells, subthreshold concentrations of FSK (cAMP) and ATP (Ca2+) synergistically increased Ca2+i and stimulated DRA activity with both being blocked by BAPTA-AM pretreatment. Diarrheal diseases, such as bile acid diarrhea, in which both cAMP and Ca2+ are elevated, are likely to be associated with stimulated DRA activity contributing to increased anion secretion, whereas separation of DRA from Na+/H+ exchanger isoform-3 (NHE3) contributes to reduced NaCl absorption.NEW & NOTEWORTHY The BB Cl-/[Formula: see text] exchanger DRA takes part in both neutral NaCl absorption and stimulated anion secretion. Using intestinal cell line, Caco-2/BBE high concentrations of cAMP and Ca2+ individually stimulated DRA activity, whereas low concentrations, which had no/minimal effect, synergistically stimulated DRA activity that required a synergistic increase in intracellular Ca2+. This study increases understanding of diarrheal diseases, such as bile salt diarrhea, in which both cAMP and elevated Ca2+ are involved."xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpcell.00523.2022"xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/author | "Lin R."xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/author | "Singh V."xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/author | "Sarker R."xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/author | "Donowitz M."xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/author | "Tse C.M."xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/name | "Am J Physiol Cell Physiol"xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/pages | "C1263-C1273"xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/title | "SLC26A3 (DRA) is stimulated in a synergistic, intracellular Ca2+-dependent manner by cAMP and ATP in intestinal epithelial cells."xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://purl.uniprot.org/core/volume | "324"xsd:string |
| http://purl.uniprot.org/citations/37154494 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37154494 |
| http://purl.uniprot.org/citations/37154494 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37154494 |
| http://purl.uniprot.org/uniprot/#_B4DUH7-mappedCitation-37154494 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37154494 |
| http://purl.uniprot.org/uniprot/#_P40879-mappedCitation-37154494 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37154494 |
| http://purl.uniprot.org/uniprot/#_Q75N04-mappedCitation-37154494 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37154494 |
| http://purl.uniprot.org/uniprot/#_Q6MZW7-mappedCitation-37154494 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37154494 |
| http://purl.uniprot.org/uniprot/P40879 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37154494 |
| http://purl.uniprot.org/uniprot/Q6MZW7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37154494 |
| http://purl.uniprot.org/uniprot/Q75N04 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37154494 |
| http://purl.uniprot.org/uniprot/B4DUH7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37154494 |