Inhibitory effects of copiamycin A, a macrocyclic lactone antibiotic, on gastric H+,K(+)-ATPase, acid secretion and ulcer formation.
When 17 macrocyclic lactone antibiotics were examined for their abilities to inhibit gastric H+,K(+)-ATPase, copiamycin A was found to have the strongest and relatively specific activity with IC50s of 15.7 micrograms/ml and greater than 100 micrograms/ml against the hog gastric H+,K(+)-ATPase and the dog kidney Na+,K(+)-ATPase, respectively. Furthermore, this antibiotic inhibited the histamine-induced gastric acid secretion in the isolated gastric mucosal membrane of guinea pigs and the gastric ulcer formation in pylorus-ligated rats.
Hamagishi
Y
Y
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
Kawano
K
K
Kamei
H
H
Oki
T
T
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D006168:Guinea Pigs; D017506:H(+)-K(+)-Exchanging ATPase; D007668:Kidney / Q000201:enzymology; D007783:Lactones / Q000494:pharmacology*; D011708:Pylorus / Q000601:surgery; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013276:Stomach Ulcer / Q000378:metabolism / Q000517:prevention & control*; D013552:Swine
D000900:Anti-Bacterial Agents; D007783:Lactones; C000507:copiamycin; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase