Adaptation by the collecting duct to an exogenous acid load is blunted by deletion of the proton-sensing receptor GPR4.

Adaptation by the collecting duct to an exogenous acid load is blunted by deletion of the proton-sensing receptor GPR4. Am J Physiol Renal Physiol. 2015 May 13;:ajprenal.00507.2014 Authors: Sun X, Stephens L, DuBose TD, Petrovic S Abstract We previously reported that the deletion of the pH sensor GPR4 causes a non-gap metabolic acidosis and defective net acid excretion (NAE) in the GPR4 knockout mouse (GPR4-/-). Since the major regulatory site of NAE in the kidney is the collecting duct (CD), we examined acid-base transport proteins in intercalated cells of CD and found comparable mRNA expression of kAE1 (anion exchanger 1), pendrin, and a4 subunit of H+-ATPase in GPR4-/-vs.+/+. However, NH4Cl loading elicited adaptive doubling of AE1 mRNA in GPR4+/+, but a 50% less pronounced response in GPR4-/-. In GPR4+/+, NH4Cl loading evoked a cellular response characterized by an increase in AE1-labeled and a decrease in pendrin-labeled intercalated cells (ICs) similar to what was reported in rabbits and rats. This response did not occur in GPR4 -/-. Microperfusion experiments demonstrated that the activity of the basolateral Cl-/HCO3- exchanger, kAE1, in CDs isolated from GPR4-/-, failed to increase with NH4Cl loading, in contrast to the increase observed in GPR4+/+. Therefore, the deficiency of GPR4 blunted, but did not eliminate the adaptive response to an acid load, suggesting a compensatory response from other pH/CO2/bicarbonate sensors. I...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research