Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson's neurodegeneration

Eur J Pharmacol. 2003 Aug 8;474(2-3):223-6. doi: 10.1016/s0014-2999(03)02080-6.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzothiazoles
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / metabolism*
  • Neuropeptides*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*
  • Pramipexole
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Vesicles / drug effects*
  • Synaptic Vesicles / metabolism
  • Thiazoles / pharmacology*
  • Thiazoles / therapeutic use
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins

Substances

  • Benzothiazoles
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Neuropeptides
  • Thiazoles
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins
  • Pramipexole
  • Dopamine