Effect of stilbene derivatives on gastric H+, K(+)-ATPase.
The effect of naturally occurring hydroxystilbene, 3,3',4,5-tetrahydroxystilbene (piceatanol), and its derivatives on gastric H+, K(+)-ATPase was studied. Piceatanol inhibited H+, K(+)-ATPase in a dose-dependent manner. The 50% inhibition value was 4.3 x 10(-6) M. It was found from the kinetic study that the inhibition of the enzyme by piceatanol was competitive with respect to ATP and was noncompetitive with respect to K+. Piceatanol also effectively inhibited gastric acid secretion. However, methylation of phenolic hydroxy groups of piceatanol resulted in a complete loss of inhibition of the enzyme and acid secretion, suggesting the role of phenolic hydroxy groups in the inhibition. The study on hydroxystilbene derivatives also showed that phenolic hydroxy groups are important in the interaction with H+, K(+)-ATPase and that stilbenes with neighbouring hydroxy groups are the most effective inhibitors.
Murakami
S
S
Research Center, Taisho Pharmaceutical Co. Ltd, Saitama, Japan.
Arai
I
I
Muramatsu
M
M
Otomo
S
S
Baba
K
K
Kido
T
T
Kozawa
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007700:Kinetics; D011188:Potassium / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013267:Stilbenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine
D054328:Proton Pump Inhibitors; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium