The effect of microtubular inhibitors on transport of α-aminoisobutyric acid. Inhibition of uphill transport without changes in transmembrane gradients of Na⁺, K⁺, or H⁺

A prior study indicated that vinca alkaloids partially inhibit the uphill transport of α-aminoisobutyric acid in Ehrlich ascites tumor cells. Maximum inhibition reduced the steady-state α-aminoisobutyric acid distribution ratio by only 25% leaving a large residual gradient. Studies were undertaken in two independent laboratories to correlate alterations in α-aminoisobutyric acid transport induced by vinca alkaloids with electrochemical potential differences for Na⁺, K⁺, or H⁺ across the cell membrane. Vincristine reduced the transmembrane steady-state gradient for α-aminoisobutyric acid by 13% (Richmond) or 18% (Alabama), respectively. Vinblastine reduced this gradient by 14.5%. There was no concurrent change in the chemical gradients for Na⁺, K⁺, or H⁺ across the cell membrane. A small, 4.08%, increase in the Cl^- distribution ratio would not account for the much larger change in α-aminoisobutyric acid gradients on the basis of a decrease in the electrochemical potential for intracellular Na⁺. These data indicate that the decrease in the α-aminoisobutyric acid gradient across the Ehrlich ascites tumor cell membrane induced by vinca alkaloids cannot be attributed to a fall in the transmembrane electrochemical potential differences for Na⁺, K⁺, or H⁺. The data suggest a role for cellular microtubules in the uphill transport of α-aminoisobutyric acid in this cell system.