Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells

Agmatine, a product of arginine decarboxylation in mammalian cells, is beli eved to govern cell polyamines by inducing antizyme, which in turn suppress es ornithine decarboxylase (ODC) activity and polyamine uptake. However, si nce agmatine is structurally similar to the polyamines, it is possible that it exerts antizyme-independent actions on polyamine regulatory pathways. T he present study determined whether agmatine inhibited ODC activity and pol yamine transport in rat pulmonary artery endothelial cells (PAECs) by an an tizyme-dependent mechanism. Agmatine caused time-dependent reductions in OD C activity, which occurred before increases in antizyme. Interventions that suppressed proteosome function caused large increases in ODC activity but failed to attenuate inhibitory effects of agmatine. When agmatine was prese nt in the culture medium, C-14-polyamine uptake was competitively inhibited as evidenced by substantial elevations in Km values. If PAECs were incubat ed with agmatine for periods sufficient to increase antizyme, there were mo dest decreases in Vmax for putrescine and spermidine but not for spermine. These effects of agmatine on polyamine transport were insensitive to protei n synthesis inhibition. Collectively, our findings show that agmatine decre ases ODC activity and polyamine transport in PAECs, but a causal role for a ntizyme in these actions of agmatine is difficult to establish. Nevertheles s, these observations are consistent with a model in which PAECs express bo th antizyme-1 and -2, but only the latter contributes to agmatine-mediated suppression of ODC activity.