Inhibitory effect of reserpine on dopamine transporter function.
Previous studies indicate that reserpine may disrupt dopamine transporter activity. Results presented herein reveal that it also inhibits potently synaptosomal [3H]dopamine uptake. In addition, reserpine administration to rats decreased the V(max) of synaptosomal dopamine transport, as assessed ex vivo 12 h after treatment. This decrease appeared, at least in part, dissociated from concurrent inhibition of the vesicular monoamine transporter-2 (VMAT-2). In separate experiments, synaptosomal dopamine uptake did not differ between wild-type and heterozygous VMAT-2 knockout mice, and reserpine treatment did not inhibit [3H]dopamine uptake into cells heterogously expressing the human dopamine transporter. Taken together, these data suggest that reserpine may transiently alter dopamine transporter function in a noncompetitive, indirect manner.
Metzger
Ryan R
RR
Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City 84112, USA.
Brown
Jeffrey M
JM
Sandoval
Verónica
V
Rau
Kristi S
KS
Elwan
Mohamed A
MA
Miller
Gary W
GW
Hanson
Glen R
GR
Fleckenstein
Annette E
AE
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004298:Dopamine / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D026901:Membrane Transport Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D014407:Tumor Cells, Cultured; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D014316:Tritium; D012110:Reserpine; D004298:Dopamine