Low concentrations of D-amphetamine (AMPH) released [H-3]dopamine (DA)
from purified, rat brain synaptic vesicles with exponential kinetics
and a half-time of 4 min. Slight alkalinization of the vesicles by AMP
H seemed unable to account for this release. instead, it is likely tha
t AMPH partially inhibits DA uptake after which DA escapes by an uptak
e-independent pathway. At high concentrations the proton gradient was
severely reduced by AMPH and DA was released with a half-time of <1 mi
n. Loss of the proton gradient was sufficient to account for this DA r
elease. These results show that low concentrations of AMPH release DA
from synaptic vesicles and suggest that release occurs by different me
chanisms at low and high AMPH concentrations.