RT Journal Article
SR Electronic
T1 Experimental Evaluation of Proposed Small-Molecule Inhibitors of Water Channel Aquaporin-1
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 686
OP 693
DO 10.1124/mol.116.103929
VO 89
IS 6
A1 Esteva-Font, Cristina
A1 Jin, Byung-Ju
A1 Lee, Sujin
A1 Phuan, Puay-Wah
A1 Anderson, Marc O.
A1 Verkman, A.S.
YR 2016
UL http://molpharm.aspetjournals.org/content/89/6/686.abstract
AB The aquaporin-1 (AQP1) water channel is a potentially important drug target, as AQP1 inhibition is predicted to have therapeutic action in edema, tumor growth, glaucoma, and other conditions. Here, we measured the AQP1 inhibition efficacy of 12 putative small-molecule AQP1 inhibitors reported in six recent studies, and one AQP1 activator. Osmotic water permeability was measured by stopped-flow light scattering in human and rat erythrocytes that natively express AQP1, in hemoglobin-free membrane vesicles from rat and human erythrocytes, and in plasma membrane vesicles isolated from AQP1-transfected Chinese hamster ovary cell cultures. As a positive control, 0.3 mM HgCl2 inhibited AQP1 water permeability by >95%. We found that none of the tested compounds at 50 µM significantly inhibited or increased AQP1 water permeability in these assays. Identification of AQP1 inhibitors remains an important priority.