Add time:08/27/2019         Source:sciencedirect.com

A new compound, 1-(2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2-c]quinoline (DBM-819), inhibited gastric H+/K+ ATPase in the rabbit (EC 3.6.1.3) with an IC50 value of 5 μM. However, DBM-819 was a weak inhibitor of kidney Na+/K+ ATPase in the dog, indicating that it has selectivity for the gastric H+/K+ ATPase. The inhibition was reversible and non-competitive with respect to the activating cation K+. The presence of dithiothreitol did not protect the H+/K+ ATPase from inactivation. The inhibition by DBM-819 was potentiated by acid pretreatment of the compound, suggesting that DBM-819 is converted into a more active intermediate under acidic conditions. The results suggest that DBM-819 is a potent, selective and reversible inhibitor of gastric H+/K+ ATPase, and that the essential cysteine residue may not be involved in the DBM-819-mediated inactivation of gastric H+/K+ ATPase.

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