Deletion of the pH sensor GPR4 decreases renal acid excretion

Xuming Sun, Li V. Yang, Brian C. Tiegs, Lois J Arend, Dennis W. McGraw, Raymond B. Penn, Snezana Petrovic

Research output: Contribution to journalArticle

Abstract

Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

Original languageEnglish (US)
Pages (from-to)1745-1755
Number of pages11
JournalJournal of the American Society of Nephrology
Volume21
Issue number10
DOIs
StatePublished - 2010

Fingerprint

Collecting Kidney Tubules
Acids
Kidney
Protons
Homeostasis
Kidney Cortex
G-Protein-Coupled Receptors
Acidosis
Cultured Cells
Epithelial Cells
Renal Elimination
Ligands

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Sun, X., Yang, L. V., Tiegs, B. C., Arend, L. J., McGraw, D. W., Penn, R. B., & Petrovic, S. (2010). Deletion of the pH sensor GPR4 decreases renal acid excretion. Journal of the American Society of Nephrology, 21(10), 1745-1755. https://doi.org/10.1681/ASN.2009050477

Deletion of the pH sensor GPR4 decreases renal acid excretion. / Sun, Xuming; Yang, Li V.; Tiegs, Brian C.; Arend, Lois J; McGraw, Dennis W.; Penn, Raymond B.; Petrovic, Snezana.

In: Journal of the American Society of Nephrology, Vol. 21, No. 10, 2010, p. 1745-1755.

Research output: Contribution to journalArticle

Sun, X, Yang, LV, Tiegs, BC, Arend, LJ, McGraw, DW, Penn, RB & Petrovic, S 2010, 'Deletion of the pH sensor GPR4 decreases renal acid excretion', Journal of the American Society of Nephrology, vol. 21, no. 10, pp. 1745-1755. https://doi.org/10.1681/ASN.2009050477
Sun, Xuming ; Yang, Li V. ; Tiegs, Brian C. ; Arend, Lois J ; McGraw, Dennis W. ; Penn, Raymond B. ; Petrovic, Snezana. / Deletion of the pH sensor GPR4 decreases renal acid excretion. In: Journal of the American Society of Nephrology. 2010 ; Vol. 21, No. 10. pp. 1745-1755.
@article{43a38ab09c6240e3849dcfc2d7680ffb,
title = "Deletion of the pH sensor GPR4 decreases renal acid excretion",
abstract = "Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.",
author = "Xuming Sun and Yang, {Li V.} and Tiegs, {Brian C.} and Arend, {Lois J} and McGraw, {Dennis W.} and Penn, {Raymond B.} and Snezana Petrovic",
year = "2010",
doi = "10.1681/ASN.2009050477",
language = "English (US)",
volume = "21",
pages = "1745--1755",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "10",

}

TY - JOUR

T1 - Deletion of the pH sensor GPR4 decreases renal acid excretion

AU - Sun, Xuming

AU - Yang, Li V.

AU - Tiegs, Brian C.

AU - Arend, Lois J

AU - McGraw, Dennis W.

AU - Penn, Raymond B.

AU - Petrovic, Snezana

PY - 2010

Y1 - 2010

N2 - Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

AB - Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

UR - http://www.scopus.com/inward/record.url?scp=77957869783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957869783&partnerID=8YFLogxK

U2 - 10.1681/ASN.2009050477

DO - 10.1681/ASN.2009050477

M3 - Article

C2 - 20798260

AN - SCOPUS:77957869783

VL - 21

SP - 1745

EP - 1755

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 10

ER -