Abstract
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 13 putative small-molecule AQP1 inhibitors reported in six recent papers, 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 CHO 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 AQP1 water permeability in these assays. Identification of AQP1 inhibitors remains an important priority.
- The American Society for Pharmacology and Experimental Therapeutics