Na(+)-coupled Cl- transport in the gastric mucosa of the guinea pig.

The Cl-/HCO3 exchange mechanism usually postulated to occur in gastric mucosa cannot account for the Na(+)-dependent electrogenic serosal to mucosal Cl- transport often observed. It was recently suggested that an additional Cl- transport mechanism driven by the Na+ electrochemical potential gradient may be present on the serosal side of the tissue. To verify this, we have studied Cl- transport in guinea pig gastric mucosa. Inhibiting the (Na+, K+) ATPase either by serosal addition of ouabain or by establishing K(+)-free mucosal and serosal conditions abolished net Cl- transport. Depolarizing the cell membrane potential with triphenylmethylphosphonium (a lipid-soluble cation), and hence reducing both the Na+ and Cl- electrochemical potential gradients, resulted in inhibition of net Cl- flux. Reduction of short-circuit current on replacing Na+ by choline in the serosal bathing solution was shown to be due to inhibition of Cl- transport. Serosal addition of diisothiocyanodisulfonic acid stilbene (an inhibitor of anion transport systems) abolished net Cl- flux but not net Na+ flux. These results are compatible with the proposed model of a Cl-/Na+ cotransport mechanism governing serosal Cl- entry into the secreting cells. We suggest that the same mechanism may well facilitate both coupled Cl-/Na+ entry and coupled HCO3-/Na+ exit on the serosal side of the tissue.