Molecular mechanisms of renal sulfate regulation.
Inorganic sulfate is an important physiological anion that is a required cofactor for sulfate conjugation reactions of both endogenous and exogenous compounds. It is necessary for the detoxification of xenobiotics and endogenous compounds (catecholamines, steroids, bile acids), for the synthesis of structural components of membranes and tissues (sulfated glycosaminoglycans), and for the biologic activity of endogenous compounds (heparin and cholecystokinin). Inorganic sulfate homeostasis is largely maintained by reabsorption in the renal proximal tubule. Sodium-dependent sulfate cotransport in the brush border membrane is of primary importance in the regulation of plasma inorganic sulfate concentrations. Altered renal reabsorption of sulfate has been observed under different physiological (age, pregnancy, low dietary intake), pathological (hypothyroidism, trace metal excess), and pharmacological conditions (treatment with nonsteroidal antiinflammatory agents). The recent identification of the sulfate transporter genes has allowed the investigation of the molecular mechanisms of altered sulfate transport. Although the regulation of sulfate homeostasis is not fully understood, recent investigations have explored the cellular mechanisms of some of these alterations. In this review, the physiological importance of inorganic sulfate, the availability of this anion, and the regulation of sulfate homeostasis are discussed.
Morris
M E
ME
Department of Pharmaceutics, State University of New York at Buffalo, Amherst 14260, USA.
Sagawa
K
K
D000375:Aging / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D026901:Membrane Transport Proteins; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076988:Sulfate Transporters; D013431:Sulfates / Q000097:blood / Q000737:chemistry / Q000378:metabolism*
D002352:Carrier Proteins; D006728:Hormones; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D013431:Sulfates