The Effect of Endothelins on Ion Transport Systems in Cultured Rat Brain Capillary Endothelial Cells

Summary

Brain capillary endothelial cells regulate the movement of ions and water across the blood-brain barrier via specific ion transport systems. Disturbances in these ion transport systems are involved in the formation of ischemic brain edema. This study describes the effects of endothelins (i.e., ET-1 and ET-3) on ion transport systems in cultured rat brain capillary endothelial cells using ⁸⁶Rb⁺ and ²²Na⁺ as markers for K⁺ and Na⁺, respectively. ET-1 stimulated K⁺ uptake and efflux with EC₅₀ values of 0.6 nM and 0.5 nM, respectively. The potencies of ET-3 on these responses were considerably lower. Both ET-1 and ET-3 stimulated Na⁺ uptake through a Na⁺/H⁺ exchange system with similar potencies (i.e., EC⁵⁰ = 0.80 nM and 1.89 nM, respectively). ET-stimulated K⁺ uptake, K⁺ efflux, and Na⁺ uptake activities were all inhibited by BQ123 (selective ET_A receptor antagonist). ET-1-stimulated K⁺ uptake and efflux, in contrast to Na⁺ uptake, were also reduced by protein kinase C inhibitors and by an intracellular Ca²⁺ chelator. The results suggest that ETs can affect the activities of ion and water transport at the blood-brain barrier through different signal transduction mechanisms.