On the role of P2X(7) receptors in dopamine nerve cell degeneration in a rat model of Parkinson's disease: studies with the P2X(7) receptor antagonist A-438079

J Neural Transm (Vienna). 2010 Jun;117(6):681-7. doi: 10.1007/s00702-010-0400-0. Epub 2010 Apr 13.

Abstract

The role of the ATP-gated receptor, P2X(7), has been evaluated in the unilateral 6-OHDA rat model of Parkinson's disease using the P2X(7) competitive antagonist A-438079. Nigral P2X(7) immunoreactivity was mainly located in microglia but also in astroglia. A-438079 partially but significantly prevented the 6-OHDA-induced depletion of striatal DA stores. However, this was not associated with a reduction of DA cell loss. Blockade of P2X(7) receptors may represent a novel protective strategy for striatal DA terminals in Parkinson's disease and warrants further future investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Adrenergic Agents / toxicity
  • Analysis of Variance
  • Animals
  • Brain / metabolism
  • Cell Count / methods
  • Chromatography, High Pressure Liquid / methods
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Glial Fibrillary Acidic Protein / metabolism
  • Homovanillic Acid / metabolism
  • Male
  • Nerve Degeneration / complications
  • Neural Pathways / metabolism
  • Oxidopamine / toxicity
  • Parkinson Disease / complications*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / etiology
  • Purinergic P2 Receptor Antagonists*
  • Pyridines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X7
  • Statistics, Nonparametric
  • Tetrazoles / therapeutic use*

Substances

  • 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine
  • Adrenergic Agents
  • Glial Fibrillary Acidic Protein
  • P2rx7 protein, rat
  • Purinergic P2 Receptor Antagonists
  • Pyridines
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Tetrazoles
  • 3,4-Dihydroxyphenylacetic Acid
  • Oxidopamine
  • Dopamine
  • Homovanillic Acid