Mammalian ion‐coupled solute transporters.

Abstract

Active transport of solutes into and out of cells proceeds via specialized transporters that utilize diverse energy-coupling mechanisms. Ion-coupled transporters link uphill solute transport to downhill electrochemical ion gradients. In mammals, these transporters are coupled to the cotransport of H+, Na+, Cl-and/or to the countertransport of K+ or OH-. By contrast, ATP-dependent transporters are directly energized by the hydrolysis of ATP. The development of expression cloning approaches to select cDNA clones solely based on their capacity to induce transport function in Xenopus oocytes has led to the cloning of several ion-coupled transporter cDNAs and revealed new insights into structural designs, energy-coupling mechanisms and physiological relevance of the transporter proteins. Different types of mammalian ion-coupled transporters are illustrated by discussing transporters isolated in our own laboratory such as the Na+/glucose co-transporters SGLT1 and SGLT2, the H+-coupled oligopeptide transporters PepTi and PepT2, and the Na+-and K+-dependent neuronal and epithelial high affinity glutamate transporter EAACI. Most mammalian ioncoupled organic solute transporters studied so far can be grouped into the following transporter families: (1) the predominantly Na+-coupled transporter family which includes the Na+/glucose cotransporters SGLT1, SGLT2, SGLT3 (SAAT-pSGLT2) and the inositol transporter SMIT, (2) the Na+-and OP-coupled transporter family which includes the neurotransmitter transporters of y-aminobutyric acid (GABA), serotonin, dopamine, norepinephrine, glycine and proline as well as transporters of f-amino acids, (3) the Na+-and K+-dependent glutamate/neurotransmitter family which includes the high affinity glutamate transporters EAAC1, GLT-1, GLAST, EAAT4 and the neutral amino acid transporters ASCTI and SATTI reminiscent of system ASC and (4) the H+-coupled oligopeptide transporter family which includes the intestinal H+-dependent oligopeptide transporter PepTI.

Ventricular Choline Transport

“…8). Low Na ϩ conditions produced a significant reduction in the uptake of proline, which is mediated by a Na ϩ /proline cotransporter (52,53), and of methotrexate, an organic anion handled by transporters (54,55) dependent upon a counterion gradient that is maintained by a Na ϩ /dicarboxylate cotransporter (56,57). However, lowering of Na ϩ was without effect on CP choline uptake, demonstrating choline uptake across the apical CP membrane is not directly coupled to Na ϩ influx (Fig.…”

Intestinal Sodium Glucose Cotransporter 1 Inhibition Enhances Glucagon-Like Peptide-1 Secretion in Normal and Diabetic Rodents

“…Sodium glucose cotransporter (SGLT) 2 is predominantly located on the apical side of renal proximal tubules and plays a critical role in glucose reabsorption from glomerular filtrates (Kanai et al, 1994a;Hediger et al, 1995;You et al, 1995;Abdul-Ghani et al, 2013). SGLT2 inhibitors, the newest class of OADs, lower plasma glucose levels independent of insulin action by inhibiting renal glucose reabsorption (Oku et al, 1999(Oku et al, , 2000Arakawa et al, 2001;Ueta et al, 2005).…”

Regulation of renal glucose transporters during severe inflammation

“…More distal segments reabsorb almost all of the remainder, resulting in a fractional glucose excretion of Ͻ0.1% (44,45). The sodium-dependent cotransporters (SGLTs), consisting of three subtypes, couple the uphill reabsorption of glucose from the renal tubule lumen with the downhill transport of sodium (19,20). In the early part of the proximal tubule (S1 segment), a high-capacity/lowaffinity transporter called SGLT2 mediates apical glucose uptake with a Na ϩ -glucose stoichiometry of 1:1.…”