Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of nolinium bromide [2-(3,4-dichlorophenylamino)quinolizium bromide], which acts as a K+ antagonist in the gastric H+ +K+-dependent ATPase reaction, was investigated at the level of 32P-labelled intermediates of the gastric ATPase reaction. A concentration-dependent effect of nolinium bromide was observed on the concentrations of phosphorylated intermediates. At low (up to 50 microM) concentrations the drug did not interfere with the concentrations of intermediates but exhibited a competition with K+ at the level of both 32P-labelled intermediates and hydrolysis of ATP at pH 7.0. Similar competition was noted in the H+ +K+-dependent ATPase reaction. Low nolinium bromide concentrations also drastically slowed the enzyme turnover. The concentrations of the intermediates were lowered appreciably between 50 microM- and 100 microM-nolinium bromide without affecting the ATP hydrolysis, and the effects were independent of pH. Similar to the effects at pH 7.0, the drug also exhibited competition with K+ in lowering the E approximately P concentration at pH 5.0. A dramatic effect of pH on the K+-sensitivity as well as on turnover of the 32P-labelled intermediates was observed. Although the concentrations of intermediates remained nearly unaltered at various pH values, the K+-stimulated hydrolysis of ATP showed an optimum at pH 7.0 with sharp declines at pH 5 and 8. The data suggest a critical involvement of H+ in the conversion of the K+-insensitive E1 approximately P into the K+-sensitive E2 approximately P form of the enzyme. Nolinium bromide appears to function as a K+ analogue and seems to block the entry of K+ at the K X E2 step, thereby interfering with the enzyme turnover.
 ...
PMID:Reaction mechanism of the gastric H+ +K+-dependent ATPase. Effects of inhibitor and pH. 303 53

Nolinium bromide [2-(3,4-dichlorophenyl amino)-quinolizium bromide] inhibits histamine-stimulated gastric acid secretion by bullfrog gastric mucosa in vitro. Nolinium bromide was effective from both the secretory and the nutrient sides of the chambered mucosa. The inhibitory effects of secretory but not the nutrient nolinium bromide could be largely reversed by elevating the concentration of K+ of the secretory solution. The mechanisms of the inhibitory effects of nutrient nolinium bromide appeared to be different than those from the secretory side. Gastric microsomes highly enriched in H+, K+-ATPase activity (which has been identified as the proton pump) were used to elucidate the mechanism of nolinium bromide action. Nolinium bromide inhibits in a dose-dependent manner both the gastric H+, K+-ATPase activity and H+ uptake ability of the microsomes. Increasing concentrations of K+ could reverse the nolinium bromide inhibition of both the H+, K+-ATPase activity and vesicular H+ transport. The data strongly suggest that nolinium bromide interferes primarily with the K+-dependent phosphatase step and thereby reduces the turnover of the enzyme. The data have been discussed in the light of our present day knowledge on gastric H+ transport.
 ...
PMID:Mechanism of gastric antisecretory effects of nolinium bromide. 630 5

Nolinium bromide inhibits gastric acid secretion and gastrointestinal smooth muscle contraction. While the compound's gastric antisecretory action has been attributed in part to inhibition of gastric adenylate cyclase and the gastric proton-transport ATPase, the mechanism of nolinium bromide's relaxant effect on smooth muscle has not been elucidated. We have determined that nolinium bromide inhibits contraction of vascular smooth muscle, using isolated rabbit aortic strips. This report characterizes the specificity of this inhibition (by using several agonists) and its Ca2+ dependence (by using contractile conditions of known dependence on various Ca2+ pools). Nolinium bromide (50-200 microM) was a reversible, insurmountable inhibitor of contractions induced by Ca2+ (in 40 mM KC1 depolarizing medium) and norepinephrine, with IC50 values of 96 and 118 microM, respectively, for suppression of maximum contractile force. Contractions in response to Asn1Val5-angiotensin II in both 2.5 mM Ca2+ and 0 mM Ca2+ medium were also inhibited (IC50 value = 110 microM under both conditions). Initial contraction rates for all these conditions were depressed by nolinium bromide. Nolinium bromide inhibited equally the phasic (internal Ca2+-dependent) and tonic (external Ca2+-dependent) components of norepinephrine-induced contractions. These results extend the muscle relaxant profile of nolinium bromide to include, albeit with low potency, vascular smooth muscle, and show that its potency is similar in inhibiting the contractile response to three different stimuli: angiotensin II, Ca2+, and norepinephrine.
 ...
PMID:Effect of nolinium bromide on vascular smooth muscle. 646 55