Chloride transport of frog gastric fundus: effects of omeprazole

Omeprazole (10(-4) M) inhibited H+ secretion and increased potential difference (PD), resistance, and short-circuit current (Isc) in chambered bullfrog gastric mucosa, but the electrical changes developed only in tissues previously exposed to histamine. Net chloride transport (JnetCl) did not change after omeprazole under short-circuited conditions, and Isc increased to become equal to JnetCl. Under open-circuit conditions, JnetCl was reduced by 38%, the decrement attributable to the concomitant increase in PD, as evidenced by a linear relationship between JnetCl and PD in omeprazole-treated mucosae clamped to different PD (0-45 mV). The effect of omeprazole on PD and Isc could be blocked by metiamide and was absent in spontaneously resting tissues. HEPES nutrient solutions did not alter the electrical response or Cl- transport after omeprazole. In Na+-free solutions, omeprazole induced only a transient rise in PD and Isc. We conclude that omeprazole uncouples H+ and Cl- secretion. This Cl- secretion is electrogenic and dependent upon stimulation by histamine. Both Na+ and HCO3- seem to be involved in movement of Cl- across the basolateral membrane.