RT Journal Article
SR Electronic
T1 Deletion of the pH Sensor GPR4 Decreases Renal Acid Excretion
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 1745
OP 1755
DO 10.1681/ASN.2009050477
VO 21
IS 10
A1 Sun, Xuming
A1 Yang, Li V.
A1 Tiegs, Brian C.
A1 Arend, Lois J.
A1 McGraw, Dennis W.
A1 Penn, Raymond B.
A1 Petrovic, Snezana
YR 2010
UL http://jasn.asnjournals.org/content/21/10/1745.abstract
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.