Role of Na1/H1 exchanger NHE3 in nephron function: micropuncture studies with S3226, an inhibitor of NHE3 VOLKER VALLON,1 JAN-ROBERT SCHWARK,2 KERSTIN RICHTER,1 AND MAX HROPOT2

Vallon, Volker, Jan-Robert Schwark, Kerstin Richter, and Max Hropot. Role of Na1/H1 exchanger NHE3 in nephron function: micropuncture studies with S3226, an inhibitor of NHE3. Am. J. Physiol. Renal Physiol. 278: F375–F379, 2000.—Na1/H1 exchanger NHE3 is expressed in the luminal membrane of proximal tubule and thin and thick ascending limb of Henle’s loop. To further define its role, the novel NHE3 inhibitor S3226 was employed in micropuncture experiments in nephrons with superficial glomeruli of anesthetized rats. Microperfusion of proximal convoluted tubule with S3226 revealed a dose-dependent inhibition of reabsorption (IC50 of 4–5 μM) with a maximum inhibition of 30% for fluid and Na1. During microperfusion of Henle’s loop (last superficial proximal to first superficial distal tubular loop), no effect of S3226 (10 or 30 μM) on the reabsorption of fluid or Na1 was observed. Finally, S3226 (30 μM) left the tubuloglomerular feedback response unaltered as determined by the fall in proximal tubular stop-flow pressure in response to increasing loop of Henle perfusion rate. These studies indicate that NHE3 significantly contributes to fluid and Na1 reabsorption in proximal convoluted tubule. NHE3 appears not to significantly contribute to fluid or Na1 reabsorption in the loop of Henle (including the S3 segment of proximal tubule) or macula densa control of nephron filtration.