Inhibition of gastric H+,K+-ATPase by new dihydropyrazole derivative KYY-008.
Biochem Biophys Res Commun
; 567: 177-182, 2021 08 27.
Article
em En
| MEDLINE
| ID: mdl-34166915
The gastric proton pump (H+,K+-ATPase) responsible for the H+ secretion of gastric acid is an essential therapeutic target for acid-related diseases. H+,K+-ATPase belongs to a P2-type ATPase family. Here, we examined the effects of a newly synthesized dihydropyrazole derivative KYY-008 on the H+,K+-ATPase. KYY-008 concentration-dependently inhibited the enzyme activity of the ATPase in the membrane fractions prepared from isolated hog gastric mucosa and from human kidney HEK293 cells in which gastric H+,K+-ATPase is exogenously expressed. The IC50 values in these samples were 3.4 µM and 3.7 µM, respectively. In addition, KYY-008 significantly inhibited the H+,K+-ATPase-derived H+ uptake into the tightly sealed vesicles prepared from the hog gastric mucosa. In contrast, KYY-008 has no effect on the activities of other P2-type ATPases such as Na+,K+-ATPase and Ca2+-ATPase. KYY-008 did not change the ionic currents of voltage-dependent Ca2+ channels, that were potential targets for some dihydropyrazole derivatives. Together, we discovered a new dihydropyrazole derivative which acts as a selective inhibitor of gastric H+,K+-ATPase.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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ATPase Trocadora de Hidrogênio-Potássio
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Inibidores da Bomba de Prótons
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article