Deletion of the pH sensor GPR4 decreases renal acid excretion.
Publication/Presentation Date
10-1-2010
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.
Volume
21
Issue
10
First Page
1745
Last Page
1755
ISSN
1533-3450
Published In/Presented At
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 : JASN, 21(10), 1745–1755. https://doi.org/10.1681/ASN.2009050477
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
20798260
Department(s)
Administration and Leadership
Document Type
Article