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Article: Loss of the secretin receptor impairs renal bicarbonate excretion and aggravates metabolic alkalosis during acute base-loading

TitleLoss of the secretin receptor impairs renal bicarbonate excretion and aggravates metabolic alkalosis during acute base-loading
Authors
Issue Date1-Sep-2022
PublisherAmerican Society of Nephrology
Citation
Journal of the American Society of Nephrology, 2023, v. 236, p. 55-57 How to Cite?
Abstract

Background 

The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the β-intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the β-intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid–base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis.

Methods 

We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release.

Results 

In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release.

Conclusions 

Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.


Persistent Identifierhttp://hdl.handle.net/10722/329185
ISSN
2023 Impact Factor: 10.3
2023 SCImago Journal Rankings: 3.409
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBerg, P-
dc.contributor.authorJensen, T-
dc.contributor.authorAndersen, JF-
dc.contributor.authorSorensen, MV-
dc.contributor.authorWang, T-
dc.contributor.authorMalte, H-
dc.contributor.authorChow, BK-
dc.contributor.authorLeipziger, J -
dc.date.accessioned2023-08-05T07:55:56Z-
dc.date.available2023-08-05T07:55:56Z-
dc.date.issued2022-09-01-
dc.identifier.citationJournal of the American Society of Nephrology, 2023, v. 236, p. 55-57-
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/329185-
dc.description.abstract<h3>Background </h3><p>The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the <em>β</em>-intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the <em>β</em>-intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid–base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis.</p><h3>Methods </h3><p>We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release.</p><h3>Results </h3><p>In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release.</p><h3>Conclusions </h3><p>Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.</p>-
dc.languageeng-
dc.publisherAmerican Society of Nephrology-
dc.relation.ispartofJournal of the American Society of Nephrology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleLoss of the secretin receptor impairs renal bicarbonate excretion and aggravates metabolic alkalosis during acute base-loading-
dc.typeArticle-
dc.identifier.doi10.1681/ASN.0000000000000173-
dc.identifier.volume236-
dc.identifier.spage55-
dc.identifier.epage57-
dc.identifier.eissn1533-3450-
dc.identifier.isiWOS:000852987800061-
dc.publisher.placeHOBOKEN-
dc.identifier.issnl1046-6673-

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