A cyclic GMP‐dependent housekeeping Cl− channel in rabbit gastric parietal cells activated by a vasodilator ecabapide

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Abstract
The membrane potential of rabbit gastric parietal cells is dominated by a Cl− channel with a sub‐picosiemens single channel conductance in the basolateral membrane. The effects of 3‐[[[2‐(3,4‐dimethoxyphenyl)ethyl]carbamoyl]methyl]amino‐N‐methylbenzamide (DQ‐2511: ecabapide), a vasodilator, on the opening of this Cl− channel, the cyclic GMP content and the intracellular free Ca2+ concentration ([Ca2+]i) of parietal cells were investigated by whole‐cell patch‐clamp technique, enzyme immunoassay and Fura 2‐fluorescence measurement. Ecabapide stimulated the opening of the Cl− channel as determined by the reversal potential. This stimulation was concentration‐dependent, and its EC50 value was 0.2 μm. Both the basal and ecabapide‐induced openings of the channel were inhibited by 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB, 500 μm), a Cl− channel blocker. Another Cl− channel blocker, niflumic acid (500 μm) was much less effective. The power spectra of the currents before and after the addition of ecabapide (10 μm) were analysed. Both spectra contained only one Lorentzian (1/f2) component. 6‐Anilino‐5,8‐quinolinedione (LY83583; 5 μm), which prevents activation of soluble guanylate cyclase, significantly inhibited both the basal and ecabapide (10 μm)‐induced openings of the Cl− channel. Ecabapide (0.01 −100 μm) concentration‐dependently elevated the cyclic GMP content in the parietal cell‐rich suspension. The EC50 value was 0.2 μm. In single Fura 2‐loaded parietal cells, ecabapide (10–100 μm) did not increase [Ca2+]i. These results indicate that ecabapide stimulates an intracellular production of cyclic GMP in the parietal cell without increasing [Ca2+]i, and leads to an activation of the housekeeping Cl− channel.

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