Epigallocatechin-3-gallate is an inhibitor of Na+, K(+)-ATPase by favoring the E1 conformation.
Four catechins, epigallocatechin-3-gallate, epigallocatechin, epicatechin-3-gallate, and epicatechin, inhibited activity of the Na(+),K(+)-ATPase. The two galloyl-type catechins were more potent inhibitors, with IC(50) values of about 1 microM, than were the other two catechins. Inhibition by epigallocatechin-3-gallate was noncompetitive with respect to ATP. Epigallocatechin-3-gallate reduced the affinity of vanadate, shifted the equilibrium of E1P and E2P toward E(1)P, and reduced the rate of the E1P to E2P transition. Epigallocatechin-3-gallate potently inhibited membrane-embedded P-type ATPases (gastric H+, K(+)-ATPase and sarcoplasmic reticulum Ca(2+)-ATPase) as well as the Na(+),K(+)-ATPase, whereas soluble ATPases (bacterial F(1)-ATPase and myosin ATPase) were weakly inhibited. Solubilization of the Na(+),K(+)-ATPase with a nonionic detergent reduced sensitivity to epigallocatechin-3-gallate with an elevation of IC50 to 10 microM. These results suggest that epigallocatechin-3-gallate exerts its inhibitory effect through interaction with plasma membrane phospholipid.
Ochiai
Hideo
H
Department of Cell Biology, University of Occupational and Environmental Health, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
Takeda
Kazuo
K
Soeda
Shiori
S
Tahara
Yoshikazu
Y
Takenaka
Hitoshi
H
Abe
Kazuhiro
K
Hayashi
Yutaro
Y
Noguchi
Shunsuke
S
Inoue
Masumi
M
Schwarz
Silvia
S
Schwarz
Wolfgang
W
Kawamura
Masaru
M
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000201:enzymology; D008968:Molecular Conformation; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D013552:Swine
D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; D000254:Sodium-Potassium-Exchanging ATPase; C057580:gallocatechol