title: Effect of substituted benzimidazoles on acid secretion in isolated and enriched guinea pig parietal cells.
abstract: The inhibitory effect of the three benzimidazole derivatives timoprazole, picoprazole, and omeprazole on histamine and dbcAMP stimulated 14C-aminopyrine accumulation (= H+ secretion) has been studied in isolated and enriched guinea-pig parietal cells. All compounds tested inhibited H+ secretion in a concentration dependent manner with IC50 values of 8.5 +/- 1.9 mumol/l for timoprazole, 3.9 +/- 0.7 mumol/l for picoprazole, and 0.13 +/- 0.03 mumol/l for omeprazole. The IC50 of timoprazole, when dbcAMP was used as a stimulus, did not differ significantly from that of histamine stimulation. The type of inhibition was of a non-competitive nature. The full acid response to histamine after temporary exposure of the cells to the benzimidazoles could be restored by washing the cells twice; this suggests that the inhibition is reversible. The data - among others - indicate that the properties of the benzimidazoles described here would allow these compounds to be used as effective antisecretagogues.
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009853:Omeprazole; D012636:Secretory Rate / Q000187:drug effects
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D000632:Aminopyrine; D003994:Bucladesine; D006632:Histamine; C038402:timoprazole; D009853:Omeprazole; C028887:picoprazole