New light on the "old" chloride channel blocker DIDS.
4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) has been used as an inhibitor of anion transporters and channels since the early 1970s. A study in this issue shows that DIDS hydrolyzes in aqueous solution and then multimerizes to di-, tri-, tetra-, and pentameric polythioureas, which inhibit both the bacterial ClC-ec1 Cl(-)/H(+) exchanger and the mammalian ClC-Ka chloride channel 3-200 times more potently than DIDS itself. The DIDS tetra- and pentamer could potentially act as tethered blockers that simultaneously obstruct both chloride pathways in the dimeric CLC proteins.
Wulff
Heike
H
Department of Pharmacology, University of California, Davis, 451 Health Sciences Drive, Davis, California 95616, USA. hwulff@ucdavis.edu
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000737:chemistry* / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D016503:Drug Delivery Systems; D008958:Models, Molecular; D015394:Molecular Structure
D018118:Chloride Channels; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid