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The gastric H,K‐ATPase blocker lansoprazole is an inhibitor of chloride channels
Author(s) -
Schmarda Andreas,
Dinkhauser Patrick,
Gschwentner Martin,
Ritter Markus,
Fürst Johannes,
Scandella Elke,
Wöll Ewald,
Laich Andreas,
Rossmann Heidi,
Seidler Ursula,
Lang Florian,
Paulmichl Markus
Publication year - 2000
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 - 10.1038/sj.bjp.0703070
Subject(s) - chemistry , lansoprazole , omeprazole , chloride channel , chloride , biophysics , proton pump inhibitor , biochemistry , pharmacology , biology , organic chemistry
It was postulated that swelling dependent chloride channels are involved in the proton secretion of parietal cells. Since omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are structurally related to phenol derivatives known to block swelling dependent chloride channels, we set out to test, whether these substances – which are known to block the H,K‐ATPase – could also lead to an inhibition of swelling‐dependent chloride channels. Swelling‐dependent chloride channels – characterized in many different cell types – show highly conserved biophysical and pharmacological features, therefore we investigated the effect of omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 on swelling‐dependent chloride channels elicited in fibroblasts, after the reduction of the extracellular osmolarity. Omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are able to block swelling‐dependent chloride channels (IClswell). Lansoprazole and its protonated metabolite AG2000 act on at least two different sites of the IClswell protein: on an extracellular site which seems to be in a functional proximity to the nucleotide binding site, and on an intracellular site which allows the formation of disulfide‐bridges. The inhibition of the proton pump and the simultaneous blocking of chloride channels by omeprazole, lansoprazole and its acid activated sulphenamide form AG2000, as described here could be an effective mode to restrict proton secretion in parietal cells.British Journal of Pharmacology (2000) 129 , 598–604; doi: 10.1038/sj.bjp.0703070