Biomedical Engineering Reference
In-Depth Information
O
O
HN
HO
Cl
O
O
S
NH
2
7, Furosemide
Cl
Cl
O
HO
O
O
8, Ethacrynic acid
-
O
O
S
O
O
S
O
O
-
9, Stilbene disulfonate
4.3 Agents Acting on Epithelial Chloride Channels
Chloride permeation through CFTR channel in epithelial cells can be inhibited
by a broad range of organic anions that enter the pore from its cytoplasmic end
and physically occlude it [
169
,
170
]. Some of the important examples of such
anions may be diphenylamine carboxylate (10)[
171
], gluconate (11)[
172
], and
glibenclamide (12)[
173
]. The interaction of the anions with CFTR channel
involves electrostatic interaction with a positively charged amino acid side chain
that lines the pore, K95 [
174
]. The CFTR channel has also been found to be
potentially inhibited by arachidonic acid (13)[
175
], involving the electrostatic
interaction with positively charged amino acid side chains located within the
chloride ion permeation pathway K95 and R303 [
176
]. While K95 is located in
the first transmembrane region of the CFTR protein and is supposed to form part
of the wider inner vestibule of the channel pore [
174
], R303 is thought to be situated
at the very intracellular end of the fifth transmembrane region to be the part of the
