Arachidonic acid and prostaglandin E2 activate small‐conductance Cl‐ channels in the basolateral membrane of rabbit parietal cells.

1. Cl‐ channels in the basolateral membrane of non‐stimulated parietal cells in isolated rabbit gastric glands were studied by patch‐clamp and noise analysis techniques. 2. Voltage‐independent whole‐cell currents were recorded from parietal cells equilibrated with Cl(‐)‐containing solutions. Upon reducing the Cl‐ concentration of the basolateral bathing solution, the current‐voltage curve was rapidly shifted to the right. The reversal potential changed according to changes in the equilibrium potential for Cl‐. 3. A Cl‐ channel blocker, 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB) inhibited whole‐cell Cl‐ currents. The half‐maximal inhibitory concentration of NPPB was 300 microM, and the inhibition was reversible (at less than or equal to 200 microM). Another Cl‐ channel blocker, 4‐acetamido‐4'‐isothiocyanatostilbene‐2,2'‐dilsulphonic acid or diphenylamine‐2‐carboxylate was much less effective. 4. The power spectra of whole‐cell Cl‐ current fluctuations contained one Lorentzian component. The single Cl‐ channel conductance was estimated to be 0.35 pS by the variance noise analysis, which is in agreement with the value obtained by a method of power spectrum analysis (0.29 pS). 5. The addition of arachidonic acid (10 microM) to the basolateral medium markedly increased the whole‐cell Cl‐ current. The combined application of a cyclo‐oxygenase inhibitor, indomethacin (50 microM), and a lipoxygenase inhibitor, esculetin (100 microM), increased the Cl‐ current, whereas the administration of a phospholipase A2 inhibitor, mepacrine (100 microM), significantly decreased the whole‐cell Cl‐ current. 6. A sizeable increase in the whole‐cell Cl‐ current was also induced by a metabolite of arachidonic acid, prostaglandin E2 (10 microM), but not by leukotriene B4 (5 microM) or D4 (10 microM). 7. The present study has shown that small‐conductance Cl‐ channels are present in the basolateral membrane of rabbit parietal cells, and that the channel was functionally regulated by arachidonic acid and prostaglandin E2.