Inhibition of guinea pig gastric microsomal potassium-stimulated ATPase by nolinium bromide.
Although nolinium bromide (NB) [2-(3,4-dichlorophenylamino)-quinolizinium bromide] inhibited histamine-stimulated acid secretion in vivo in the pylorus-ligated guinea pig, no inhibition of basal or histamine-stimulated acid secretion from the isolated guinea pig gastric fundic disk was observed at serosal or mucosal concentrations from 0.1 to 200 microM. NB did not inhibit carbonic anhydrase in whole stomach homogenates of guinea pig, but did inhibit the potassium-stimulated gastric microsomal ATPase. The IC50 value (compound concentration giving 50% inhibition of the rate of ATP hydrolysis) for the net stimulated reaction (activity with KCl minus activity without KCl) was 65 microM (95% confidence limits = 42-101 microM). The basal reaction (no added KCl) was not inhibited. Inhibition of ATPase by NB was not due to its bromide ion, since NaBr did not, while the chloride analog of NB did, inhibit the enzyme. It was concluded that NB has no direct histamine-H2 receptor blocking activity. Whether ATPase inhibition contributes to its gastric acid antisecretory property is uncertain because of the lack of inhibitory activity in the isolated gastric disk assay.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D002256:Carbonic Anhydrases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism; D005748:Gastric Fundus / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D017506:H(+)-K(+)-Exchanging ATPase; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D011807:Quinolizines / Q000494:pharmacology*; D013270:Stomach / Q000201:enzymology*
D000814:Aniline Compounds; D011807:Quinolizines; D006632:Histamine; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D002256:Carbonic Anhydrases; C019025:nolinium bromide