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Blockade of swelling‐induced chloride channels by phenol derivatives
Author(s) -
Gschwentner Martin,
Jungwirth Andreas,
Hofer Sabine,
Wöll Ewald,
Ritter Markus,
Susanna Alex,
Schmarda Andreas,
Reibnegger Gilbert,
Pinggera Germar M.,
Leitinger Markus,
Frick Julian,
Deetjen Peter,
Paulmichl Markus
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.tb15364.x
Subject(s) - dids , chloride channel , extracellular , chemistry , biophysics , biochemistry , chloride , channel blocker , niflumic acid , osmotic concentration , biology , calcium , membrane , organic chemistry
1 . In NIH3T3 fibroblasts, the chloride channel involved in regulatory volume decrease (RVD) was identified as I Cln , a protein isolated from a cDNA library derived from Madin Darby canine kidney (MDCK) cells. I Cln expressed in Xenopus laevis oocytes gives rise to an outwardly rectifying chloride current, sensitive to the extracellular addition of nucleotides and the known chloride channel blockers, DIDS (4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid) and NPPB (5‐nitro‐2‐(3‐phenylpropylamino)‐benzoic acid). We set out to study whether substances structurally similar to NPPB are able to interfere with RVD. 2 . RVD in NIH3T3 fibroblasts and MDCK cells is temperature‐dependent. 3 . RVD, the swelling‐dependent chloride current and the depolarization seen after reducing extracellular osmolarity can be blocked by gossypol and NDGA (nordihydroguaiaretic acid), both structurally related to NPPB. 4 . The cyclic AMP‐dependent chloride current elicited in CaCo cells is less sensitive to the two substances tested while the calcium‐activated chloride current in fibroblasts is insensitive. 5 . The binding site for the two phenol derivatives onto I Cln seems to be distinct but closely related to the nucleotide binding site identified as G × G × G, a glycine repeat located at the predicted outer mouth of the I cln channel protein.