Differentiation among inhibitory actions of omeprazole, cimetidine, and SCN- on gastric acid secretion.
The action of the substituted benzimidazole omeprazole (H 168/68) was studied in three different in vitro preparations: the isolated guinea pig gastric mucosa, isolated intact and permeable rabbit gastric glands, and hog fundic microsomal membrane vesicles containing H+-K+-ATPase. The effects of omeprazole were compared with those of cimetidine and thiocyanate (SCN-). Under all the conditions studied, cimetidine only counteracted histamine-induced acid secretion, consonant with its H2-receptor antagonism. In contrast, omeprazole and SCN- were found not only to inhibit histamine-induced secretion but also basal acid formation and acid formation induced by dibutyryl cAMP and a high cell medium concentration of K+. Moreover, acid production induced by ATP in permeable gastric glands was antagonized by omeprazole and SCN-, whereas cimetidine was without effect. The interaction pattern of omeprazole and SCN- was differentiated by studies using the weak base antipyrine in the isolated mucosal preparation, where it was found that antipyrine could reverse the inhibition induced by SCN- but not that of omeprazole. Furthermore, omeprazole was found to inhibit the isolated H+-K+-ATPase, whereas cimetidine or SCN- was without effect. In the isolated mucosal preparation omeprazole caused an increase in K+ secretion rates in parallel with the inhibition of acid formation. This was in contrast to what was observed for cimetidine and SCN-, which exhibited no such increased K+ secretion. The results obtained from intact mucosa and isolated glands are in agreement with the ability of omeprazole to inhibit the isolated H+-K+-ATPase and thus provide evidence of a novel mechanism of action for this inhibitor.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology*; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D017506:H(+)-K(+)-Exchanging ATPase; D006632:Histamine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009853:Omeprazole; D013270:Stomach / Q000201:enzymology; D013861:Thiocyanates / Q000494:pharmacology*
D001562:Benzimidazoles; D006146:Guanidines; D013861:Thiocyanates; D000632:Aminopyrine; D002927:Cimetidine; D006632:Histamine; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole