Differences in uptake kinetics of cis-3-aminocyclohexane carboxylic acid into neurons and astrocytes in primary cultures.

The uptake of [3H]ACHC and [3H]GABA into cultured neurons and astrocytes was studied. [3H]ACHC uptake was less efficient than that of GABA in both cell types and Km values for ACHC uptake into neurons and astrocytes were 40.3 microM and 210.8 microM, respectively. The corresponding Vmax values were 0.321 and 0.405 nmol . min-1 . mg-1 cell protein, respectively. Kinetic studies of the effects of GABA on ACHC uptake and vice versa showed that GABA is a linear competitive inhibitor of ACHC uptake in both cell types with a Ki value of 15 microM. On the other hand, ACHC turned out to be a complex inhibitor of astrocytic GABA uptake being competitive at lower concentrations and non-competitive at higher concentrations. ACHC inhibited GABA uptake into neurons competitively with a Ki of 69 microM. It is concluded that ACHC acts primarily on neuronal GABA uptake sites but its uptake is much more complicated than hitherto anticipated.