Inhibitory effect of xylamine on the uptake of [3H]dopamine into isolated striatal synaptosomes of the rats.

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