Regulation of nephron water and electrolyte transport by adenylyl cyclases.
Adenylyl cyclases (AC) catalyze formation of cAMP, a critical component of G protein-coupled receptor signaling. So far, nine distinct membrane-bound AC isoforms (AC1-9) and one soluble AC (sAC) have been identified and, except for AC8, all of them are expressed in the kidney. While the role of ACs in renal cAMP formation is well established, we are just beginning to understand the function of individual AC isoforms, particularly with regard to hormonal regulation of transporter and channel phosphorylation, membrane abundance, and trafficking. This review focuses on the role of different AC isoforms in regulating renal water and electrolyte transport in health as well as potential pathological implications of disordered AC isoform function. In particular, we focus on modulation of transporter and channel abundance, activity, and phosphorylation, with an emphasis on studies employing genetically modified animals. As will be described, it is now evident that specific AC isoforms can exert unique effects in the kidney that may have important implications in our understanding of normal physiology as well as disease pathogenesis.
Dept. of Medicine, Div. of Nephrology/Hypertension, Univ. of California San Diego and VA San Diego Healthcare System; 3350 La Jolla Village Dr. (9151 San Diego, CA 92161. trieg@ucsd.edu.
Timo
T
Rieg
Donald E
DE
Kohan
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes; D007674:Kidney Diseases / Q000201:enzymology / Q000503:physiopathology; D009399:Nephrons / Q000201:enzymology* / Q000503:physiopathology; D010766:Phosphorylation; D015398:Signal Transduction; D014882:Water-Electrolyte Balance
D007527:Isoenzymes; D000242:Cyclic AMP; D000262:Adenylyl Cyclases
homeostasis; parathyroid hormone; renal disease; signaling; vasopressin