Inhibition of gastric H+,K(+)-ATPase and acid secretion by cassigarol A, a polyphenol from Cassia garrettiana Craib.
The effects of cassigarol A, a naturally occurring polyphenol, on gastric H+,K(+)-ATPase and gastric acid secretion were studied. Cassigarol A inhibited H+,K(+)-ATPase and K-stimulated p-nitrophenyl phosphatase from hog gastric mucosa with 50% inhibition of 1.2 x 10(-6) and 6.3 x 10(-6) M, respectively. The kinetic study showed that the inhibition of H+,K(+)-ATPase by cassigarol A was competitive with respect to ATP and non-competitive with respect to K+. Cassigarol A inhibited both H+,K(+)-ATPase-mediated proton transport and 2-deoxy-D-glucose-induced acid secretion. On the other hand, cassigarol A acetate, in which phenolic hydroxy groups are acetylated, was not effective in the inhibition of enzyme activity and acid secretion. These results indicate that cassigarol A is a potent inhibitor of gastric H+,K(+)-ATPase, that the anti-secretory activity of cassigarol A is related to the inhibition of H+,K(+)-ATPase and that an important moiety of cassigarol A in the interaction with the enzyme is the phenolic hydroxy groups.
Murakami
S
S
Research Center, Taisho Pharmaceutical Co. Ltd., Ohmiya, Japan.
Arai
I
I
Muramatsu
M
M
Otomo
S
S
Baba
K
K
Kido
T
T
Kozawa
M
M
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005419:Flavonoids; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000201:enzymology*; D017506:H(+)-K(+)-Exchanging ATPase; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008297:Male; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D011108:Polymers / Q000302:isolation & purification / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013552:Swine
D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; C075680:cassigarol A; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase