UPTAKE OF AGMATINE INTO RAT-BRAIN SYNAPTOSOMES - POSSIBLE ROLE OF CATION CHANNELS

Agmatine (decarboxylated arginine), an endogenous ligand for imidazoIi ne receptors, has been identified in brain where it is synthesized fro m arginine by arginine decarboxylase. Here we report a mechanism for t he transport of agmatine into rat brain synaptosomes. The uptake of ag matine was energy- and temperature-dependent and saturable with a K-m of 18.83 +/- 3.31 mM and a V-max of 4.78 +/- 0.67 nmol/mg of protein/m in. Treatment with ouabain (Na+,K+-ATPase inhibitor) or removal of ext racellular Na+ did not attenuate the uptake rate. Agmatine transport w as not inhibited by amino acids, polyamines, or monoamines, indicating that the uptake is not mediated by any amino acid, polyamine, or mono amine carriers. When we examined the effects of some ion-channel agent s on agmatine uptake, only Ca2+-channel blockers inhibited the uptake, whereas a reduction in extracellular Ca2+ increased it. In addition, some imidazoline drugs, such as idazoxan and phentolamine, were strong noncompetitive inhibitors of agmatine uptake. Thus, a selective, Na+- independent uptake system for agmatine exists in brain and may be impo rtant in regulating the extracellular concentration of agmatine.