Polyamine transport system mediates agmatine transport in mammalian cells

Agmatine is a biogenic amine with the capacity to regulate a number of nonr eceptor-mediated functions in mammalian cells, including intracellular poly amine content and nitric oxide generation. We observed avid incorporation o f agmatine into several mammalian cell lines and herein characterize agmati ne transport in mammalian cells. In transformed NIH/3T3 cells, agmatine upt ake is energy dependent with a saturable component indicative of carrier-me diated transport. Transport displays an apparent Michaelis-Menten constant of 2.5 muM and a maximal velocity of 280 pmol.min(-1).mg(-1) protein and re quires a membrane potential across the plasma membrane for uptake. Competit ion with polyamines, but not cationic molecules that utilize the y(+) syste m transporter, suppresses agmatine uptake. Altering polyamine transporter a ctivity results in parallel changes in polyamine and agmatine uptake. Furth ermore, agmatine uptake is abrogated in a polyamine transport-deficient hum an carcinoma cell line. These lines of evidence demonstrate that agmatine u tilizes, and is dependent on, the polyamine transporter for cellular uptake . The fact that this transport system is associated with proliferation coul d be of consequence to the antiproliferative effects of agmatine.