Cl(-)-ATPase in rat brain and kidney.
Cl(-)-stimulated ATPase/ATP-dependent Cl(-) pump (Cl(-)-ATPase/pump) has been found as a candidate for an active outwardly directed Cl(-) transporter in brain neurons. (1) A 520-kDa protein complex with Cl(-)-ATPase/pump activity was isolated from rat brain. It consisted of four protein subunits (51, 55, 60, and 62 kDa proteins), the 51-kDa protein being a covalent phosphorylenzyme subunit. (2) An antiserum against the 51-kDa protein inhibited Cl(-)-ATPase/pump activity. Western blot analysis showed an immunoreactive 51-kDa protein in the brain, spinal cord, and kidney. By enzyme histochemistry and immunohistochemistry, Cl(-)-ATPase-like activity or immunoreactivity was observed on the plasma membranes of brain neurons, and on the baso-lateral membranes of type A intercalated cells of renal collecting ducts. (3) Reconstituted Cl(-)-ATPase/pump activity was highest in liposomes with phosphatidylinositol-4-monophosphate. LiCl, an inhibitor of inositolphosphatase, reduced Cl(-)-ATPase activity and increased intracellular Cl(-) concentrations in cultured rat hippocampal neurons with increased phosphatidylinositol turnover. (4) In the brains of patients with Alzheimer's disease (AD), where phosphatidylinositol 4-kinase activity is reduced, Cl(-)-ATPase activity was also reduced. Thus, Cl(-)-ATPase is likely an outwardly directed ATP-dependent Cl(-) transporter that consists of four subunits and is regulated by phosphatidylinositol-4-monophosphate. Changes in Cl(-)-ATPase activity may be related to the pathophysiology of human neurodegenerative diseases. J. Exp. Zool. 289:224-231, 2001.
Inagaki
C
C
Department of Pharmacology, Kansai Medical University, Fumizono-cho 10-15, Moriguchi-City, Osaka 570-8506, Japan. inagaki@takii.kmu.ac.jp
Hattori
N
N
Kitagawa
K
K
Zeng
X T
XT
Yagyu
K
K
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D027321:Anion Transport Proteins; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D016623:Ion Pumps / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D051381:Rats
D027321:Anion Transport Proteins; D002712:Chlorides; D016623:Ion Pumps; D000251:Adenosine Triphosphatases; C031652:anion-sensitive ATPases