Vitamin D receptor (VDR) regulation of voltage-gated chloride channels by ligands preferring a VDR-alternative pocket (VDR-AP).

ABSTRACT: We have postulated that the vitamin D receptor (VDR) contains two overlapping ligand binding sites, a genomic pocket and an alternative pocket (AP), that mediate regulation of gene transcription and rapid responses, respectively. Flexible VDR + ligand docking calculations predict that the major blood metabolite, 25(OH)-vitamin D(3) (25D3), and curcumin (CM) bind more selectively to the VDR-AP when compared with the seco-steroid hormone 1α,25(OH)(2)-vitamin D(3) (1,25D3). In VDR wild-type-transfected COS-1 cells and TM4 Sertoli cells, 1,25D3, 25D3, and CM each trigger voltage-gated, outwardly rectifying chloride channel (ORCC) currents that can be blocked by the VDR antagonist 1β,25(OH)(2)-vitamin D(3) and the chloride channel antagonist (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid).

SUBMITTER: Menegaz D 

PROVIDER: S-EPMC3146250 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature