DUAL-ACTION OF COLCHICINE ON HYPERTONIC ACTIVATION OF SYSTEM-A AMINO-ACID-TRANSPORT IN VASCULAR SMOOTH-MUSCLE CELLS

Amino acid transport system A is present in many cells and tissues and is regulated by hormones and other factors, including hypertonic stre ss. System A in vascular smooth muscle cells is also activated when mi crotubules are disrupted by drugs such as colchicine. The present stud y examined the action of colchicine on hypertonic activation of system A in smooth muscle cells. In serum-free medium, activation of system A by modest (340 mOsm) hypertonicity was not affected by colchicine ad dition. However, at high osmotic stress (460 mOsm) the addition of col chicine partially blocked the activation of system A. Addition of colc hicine alone, at normal osmolarity, produced activation of system A. I n the presence of serum, colchicine action was markedly different. Col chicine consistently inhibited hypertonic activation of system A at an y degree of hypertonic stress but had no effect on system A at normal osmolarity. The action of colchicine as both an activator and inhibito r of system A implies microtubule involvement at more than one step in the intracellular regulation of system A.