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A cyclic GMP‐dependent housekeeping Cl − channel in rabbit gastric parietal cells activated by a vasodilator ecabapide
Author(s) -
Sakai Hideki,
Ikari Akira,
Kumano Eiichi,
Takeguchi Noriaki
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16077.x
Subject(s) - parietal cell , chemistry , niflumic acid , channel blocker , biophysics , medicine , endocrinology , stereochemistry , biochemistry , gastric mucosa , calcium , biology , stomach , organic chemistry
1 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 Ca 2+ concentration ([Ca 2+ ] i ) of parietal cells were investigated by whole‐cell patch‐clamp technique, enzyme immunoassay and Fura 2‐fluorescence measurement. 2 Ecabapide stimulated the opening of the Cl − channel as determined by the reversal potential. This stimulation was concentration‐dependent, and its EC 50 value was 0.2 μ m . Both the basal and ecabapide‐induced openings of the channel were inhibited by 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB, 500 μ m ), a Cl − channel blocker. Another Cl − channel blocker, niflumic acid (500 μ m ) was much less effective. 3 The power spectra of the currents before and after the addition of ecabapide (10 μ m ) were analysed. Both spectra contained only one Lorentzian (1/f 2 ) component. 4 6‐Anilino‐5,8‐quinolinedione (LY83583; 5 μ m ), which prevents activation of soluble guanylate cyclase, significantly inhibited both the basal and ecabapide (10 μ m )‐induced openings of the Cl − channel. 5 Ecabapide (0.01 −100 μ m ) concentration‐dependently elevated the cyclic GMP content in the parietal cell‐rich suspension. The EC 50 value was 0.2 μ m . 6 In single Fura 2‐loaded parietal cells, ecabapide (10–100 μ m ) did not increase [Ca 2+ ] i . 7 These results indicate that ecabapide stimulates an intracellular production of cyclic GMP in the parietal cell without increasing [Ca 2+ ] i , and leads to an activation of the housekeeping Cl − channel.