Two distinct Na؉ -coupled glucose transporters (SGLTs) with either a high or a low affinity for glucose were shown to provide reabsorption of filtered glucose in the kidney. We have previously reported the characteristics of the high affinity Na ؉ /glucose cotransporter SGLT1 from rabbit, rat, and human kidney and the low affinity Na ؉ /glucose cotransporter SGLT2 from human kidney. Because the molecular identity of SGLT2 as the kidney cortical low affinity Na ؉ to glucose coupling of 1:1 and lack of galactose transport) generally matched those of the kidney cortical low affinity system. We show that expression of rat SGLT2 mRNA is kidney specific and that it is strongly and exclusively expressed in proximal tubule S1 segments. Hybrid-depletion studies were performed to conclusively determine whether SGLT2 corresponds to the kidney cortical low affinity system. Injection of rat kidney superficial cortex mRNA into oocytes stimulated the uptake of ␣-methyl-D-glucopyranoside (2 mM) 2-3-fold. We show that hybrid depletion of this kidney RNA using an SGLT2 antisense oligonucleotide completely suppresses the uptake. These data strongly indicate that SGLT2 is the major kidney cortical low affinity glucose transporter. We therefore propose that SAAT-pSGLT2 be renamed SGLT3. Experiments addressing the expression of SGLT1 and SGLT2 mRNAs in embryonic rat kidneys reveal that the two Na ؉

Dopamine receptors in the rat kidney were characterized by homogenate binding and in vitro autoradiography using the dopamine 1 (DA1)-selective antagonist [3H]Sch 23390. [3H]Sch 23390 binding in cortical membrane preparations was saturable, stereoselective, and competed for by DA agonists and antagonists with a rank order of potency consistent with the labeling of the DA1 receptor. [3H]Sch 22390 binding was best fit to a two-site model: a high affinity-low density site (KD1 4.9 +/- 1.4 nM, Bmax 1 31.4 +/- 13.8 fmol/mg protein) and a low affinity-high density site (KD2 86.4 +/- 23.9 nM, Bmax 2 848.0 +/- 227.4 fmol/mg protein). In vitro autoradiography indicated that [3H]Sch 22390 binding sites were restricted to the cortex. High-resolution autoradiography further indicated that [3H]Sch 22390 binding sites were localized primarily on proximal tubules. Glomeruli and other vascular elements were devoid of [3H]Sch 23390 binding sites. These results suggest that DA and DA1 agonists may affect sodium excretion by a direct action on proximal tubule sodium reabsorption.

Dopamine (DA) produces a natriuretic/diuretic response in the kidney by mcnisms that are still not well understood. There is some ination that DA2 receptors may be involved in mating the effects of DA, but little is known regarding the nature of this receptor in the kidney. Autoraigaphic localation of [3Hspiperone, a DA2 anta t, i ed that high-density binding was r ic to inner meduilary ting ducts (IMCDs) Exogenous dopamine (DA) produces a natriuretic/diuretic response in a variety of species, including humans (1, 2). The natriuretic effects of DA are generally thought to be due to an increase in renal blood flow and glomerular filtration rate (1) but may include direct tubular effects since low doses of DA increase urine output and urinary sodium excretion without altering renal hemodynamics (3-5). Although the mechanism of action ofDA within the kidney is not resolved, the effects ofDA on the kidney are blocked by DA receptor antagonists (2, 6, 7). DA receptors have been classified in the central nervous system as D1 and D2 (8) and in the periphery as DA1 and DA2 (9). A great deal of evidence indicates that vascular and tubular DA1 receptors are involved in mediating the actions of DA on the kidney (6, 7). Further support for a tubular site ofaction for DA comes from autoradiographic localization of DA1 receptors in rat kidney, which indicates that the highest levels are found in the proximal tubules (10, 11).Much less is known regarding the role of DA2 receptors in mediating the renal responses to DA. Spiperone, a central nervous system D2 antagonist, blocks the DA-stimulated increase in renal blood flow and sodium excretion in isolated perfused rat kidney (4). Bromocriptine, a DA2 agonist, has been reported to increase renal blood flow and singlenephron glomerular filtration rate in the rat (12,13