Journal
BIOCHEMICAL PHARMACOLOGY
Volume 59, Issue 7, Pages 881-886Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0006-2952(99)00399-8
Keywords
H+,K+-ATPase; hinesol; inhibitor; omeprazole; So-jutsu; Atractylodis Lanceae Rhizoma; K+-pNPPase
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Hinesol, a major component of the crude drug So-jutsu (Atractylodis Lanceae Rhizoma), strongly inhibited H+,K+-ATPase activity with a IC50 value of 5.8 x 10(-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 1.6 x 10(-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 E-1 state in the presence of ATP and Mg2+ and forms the complex hinesol-H+ . E-1-ATP or hinesol . E-1-P, blocking the conformational change to the E-2 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. BIOCHEM PHARMACOL 59;7:861-886, 2000. (C) 2000 Elsevier Science Inc.
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