Omeprazole: inhibitor of both acid formation and translocation in gastric mucosa.
Omeprazole, believed to inhibit H+, K+-ATPase, was used to study acid secretion dynamics in isolated gastric mucosa. Tissue was mounted in a chamber and continuously supplied with both fresh nutrient and secretory solution (flow-through). Acid secretion was monitored on and recorded by a pH-stat microprocessor set-up. In spontaneously secreting mucosa the continuous presence of omeprazole causes a monotonic decline in secretion rate to a new lower steady state. The relationship between the inhibited steady-state acid secretion rate and omeprazole concentration is expressed by the sum of two hyperbolic functions with K1s differing by a factor of more than 100. When omeprazole is removed, the secretion rate always recovers. The amount of acid suppressed depends uniquely on omeprazole exposure: it is proportional to the exposure at low exposure and disproportionate (logarithmic) at high exposure. The index of conservation declines with omeprazole exposure, i.e. the inhibition by omeprazole ranges from conservative (no net loss of acid) to non-conservative (net loss of acid). Dithiothreitol causes the inhibition by omeprazole to be conservative (index of conservation = 0) at even higher omeprazole exposure. The index of conservation was introduced to allow for numerical evaluation of both inhibitory and stimulatory effects regardless of the magnitude of the effect. It is concluded that omeprazole acts at two different sites, possibly with inhibition by sulphoxide derivatives on the formation step and sulphide derivatives on the translocation step.
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Cardiovascular Research Institute, University of California, San Francisco 94143.
D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D009853:Omeprazole / Q000494:pharmacology*; D011892:Rana catesbeiana
D009853:Omeprazole; D004229:Dithiothreitol