Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli.
Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the Na(+)/H(+) exchanger isoform 3 (NHE3), Na(+)/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 microg/min for 20 min) that increased PT flow rate approximately 20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng x kg(-1) x min(-1) for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG II included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar H(+)-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption.
Department of Cell and Neurobiology, University of Southern California Keck School of Medicine, Los Angeles, California 90089, USA.
Anne D M
AD
Riquier-Brison
Patrick K K
PK
Leong
Kaarina
K
Pihakaski-Maunsbach
Alicia A
AA
McDonough
D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002966:Clathrin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D050610:Sodium-Phosphate Cotransporter Proteins, Type II / Q000378:metabolism*; D000099149:Ezrin
D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D002966:Clathrin; D003598:Cytoskeletal Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D018995:Myosin Heavy Chains; D012965:Sodium Chloride; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D000099149:Ezrin; C000613387:Slc9a3 protein, rat; C089785:myosin VI