INHIBITORY EFFECT OF XYLAMINE ON THE UPTAKE OF [H-3] DOPAMINE INTO ISOLATED STRIATAL SYNAPTOSOMES OF THE RATS

The synaptosomal preparations from Wistar rat striata show a Na+-depen dent, nomifensine-sensitive uptake of [H-3]dopamine ([H-3]DA). Xylamin e, a nitrogen mustard, attenuated this uptake of [H-3]DA into the syna ptosomes (IC50 = 0.2 muM). The dose-dependent reduction of [H-3]DA upt ake by xylamine indicated competitive kinetics. Action of xylamine was modified if the active transport inhibitor, ouabain or iodoacetate, w as also incubated during the pretreatment period or if the content of Na+ in medium was changed. Also, xylamine displaced the binding of [H- 3]mazindol in a correlative way with the inhibition of [H-3]DA uptake. However, the activity of Na+, K+-ATPase in synaptosomes was not modif ied by xylamine at concentrations sufficient to block the uptake of [H -3]DA. These findings suggest that xylamine has the ability to compete with the transport of [H-3]DA into striatal synaptosomes through an e ffect on the carrier instead of an action on enzymatic activity.