High‐Affinity Uptake of (RS)‐Nipecotic Acid in Astrocytes Cultured from Mouse Brain. Comparison with GABA Transport

Abstract: (RS)‐Nipecotic acid is taken up into cultured astrocytes by a saturable high‐affinity transport system with a K m , of 28.8 ± 2.8 μM and a V max of 0.294 ± 0.022 nmol × min −1 × [mg cell protein] −1 . The uptake which represents a net inward transport was sodium‐dependent, requiring translocation of one sodium ion for each molecule of nipecotic acid taken up. The most potent inhibitors of GABA uptake into astrocytes (GABA, (R)‐nipecotic acid, (3RS,4SR)‐4‐hydroxynipecotic acid, and guvacine) were shown to be potent inhibitors of nipecotic acid uptake (IC 50 ) 20, 25, 25, and 50 μm respectively), GABA being a competitive inhibitor. (S)‐2,4‐Diaminobutyric acid was a more efficient inhibitor than β‐alanine of glial uptake of (RS)‐nipecotic acid. It is concluded that astroglial uptake of (RS)‐nipecotic acid and GABA is mediated by the same transport system.