Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson's neurodegeneration.
Pramipexole is a dopamine D2/D3 receptor agonist used to treat Parkinson's disease. Both human and animal studies suggest that pramipexole may exhibit neuroprotective properties involving dopamine neurons. However, mechanisms underlying its neuroprotective effects remain uncertain. The present results reveal a novel cellular action of this agent. Specifically, pramipexole rapidly increases vesicular dopamine uptake in synaptic vesicles prepared from striata of treated rats. This effect is: (1) associated with a redistribution of vesicular monoamine transporter-2 (VMAT-2) immunoreactivity within nerve terminals; and, (2) prevented by pretreatment with the dopamine D2 receptor antagonist, eticlopride. The implications of this finding relevant to the treatment of neurodegenerative disorders are discussed.
Truong
Jannine G
JG
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Rau
Kristi S
KS
Hanson
Glen R
GR
Fleckenstein
Annette E
AE
D000818:Animals; D052160:Benzothiazoles; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism*; D009479:Neuropeptides; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D000077487:Pramipexole; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D052160:Benzothiazoles; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D013844:Thiazoles; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D000077487:Pramipexole; D004298:Dopamine