Cloning , renal distribution , and regulation of the rat Na 1 - HCO 3 2 cotransporter

Burnham, Charles E., Michael Flagella, Zhaohui Wang, Hassane Amlal, Gary E. Shull, and Manoocher Soleimani. Cloning, renal distribution, and regulation of the rat Na-HCO3 2 cotransporter. Am. J. Physiol. 274 (Renal Physiol. 43): F1119–F1126, 1998.—We recently reported the cloning and expression of a human kidney Na-HCO3 2 cotransporter (NBC-1) (C. E. Burnham, H. Amlal, Z. Wang, G. E. Shull, and M. Soleimani. J. Biol. Chem. 272: 19111– 19114, 1997). To expedite in vivo experimentation, we now report the cDNA sequence of rat kidney NBC-1. In addition, we describe both the organ and nephron segment distributions and the regulation of NBC-1 mRNA under three models of pH stress: chloride-depletion alkalosis (CDA), metabolic acidosis, and bicarbonate loading. Rat NBC-1 cDNA encodes an open reading frame of 1,035 amino acids, with 96 and 87% identity to human and salamander NBC-1, respectively. Rat NBC-1 mRNA is expressed at high levels in kidney and brain, with lower levels in colon, stomach, and heart. None appears in liver. In the kidney, NBC-1 is expressed mainly in the proximal tubule, with traces found in medullary thick ascending limb and papilla. HCO3 2 loading decreased NBC-1 mRNA levels, which were unchanged either by metabolic acidosis or by CDA.