Inhibition of H+,K+ -ATPase by hinesol, a major component of So-jutsu, by interaction with enzyme in the E1 state.

Abstract

Hinesol, a major component of the crude drug "So-jutsu" (Atractylodis Lanceae Rhizoma), strongly inhibited H+,K+-ATPase activity with a IC50 value of 5.8x10(-5) M. It also inhibited Na+,K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, and H+-ATPase activities, although the inhibition rate was lower. No effects on alkaline or acid phosphatase activities were observed. The mechanism by which hinesol inhibited H+,K+-ATPase activity was studied in detail. The inhibition was uncompetitive with respect to ATP, and it increased as the Mg2+ concentration was raised, whereas it was not affected by the K+ concentration. The activity of K+-dependent p-nitrophenyl phosphatase (K+-pNPPase), a partial reaction of H+,K+-ATPase, was inhibited by hinesol noncompetitively with respect to pNPP (IC50 value of 1.6x10(-4) M), and competitively with respect to K+, whereas it was not affected by the Mg2+ concentration. These results suggest that hinesol is a relatively specific inhibitor of H+,K+-ATPase. It appears that hinesol reacts with enzyme in the E1 state in the presence of ATP and Mg2+ and forms the complex hinesol-H+ E1-ATP or hinesol x E1-P, blocking the conformational change to the E2 state. Furthermore, hinesol enhanced the inhibitory effect of omeprazole on H+,K+-ATPase, and the inhibitory site of hinesol was different from that of omeprazole. The effect of So-jutsu as an anti-gastric ulcer agent may be ascribed to the inhibitory effect of hinesol on H+,K+-ATPase activity.

• Authors: K Satoh, F Nagai, I Kano
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 59 Issue 7 Pg. 881-6 (Apr 01 2000) ISSN: 0006-2952 [Print] England
• PMID: 10718347 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• Enzyme Inhibitors
• Ligands
• Proton Pump Inhibitors
• Sesquiterpenes
• Spiro Compounds
• hinesol
• Phosphoric Monoester Hydrolases
• 4-Nitrophenylphosphatase
• Adenosine Triphosphatases
• Omeprazole

Topics

• 4-Nitrophenylphosphatase (antagonists & inhibitors, metabolism)
• Adenosine Triphosphatases (antagonists & inhibitors, metabolism)
• Animals
• Drugs, Chinese Herbal (chemistry)
• Enzyme Inhibitors (pharmacology)
• In Vitro Techniques
• Ligands
• Medicine, Chinese Traditional
• Omeprazole (pharmacology)
• Phosphoric Monoester Hydrolases (antagonists & inhibitors, metabolism)
• Proton Pump Inhibitors
• Sesquiterpenes
• Spiro Compounds (pharmacology)
• Swine