Modulation of dopamine receptor agonist-induced rotational behavior in 6-OHDA-lesioned rats by a peptidomimetic analogue of Pro-Leu-Gly-NH2 (PLG)

Ram K. Mishra, Eric R. Marcotte, Anita Chugh, Cia Barlas, Deborah Whan, Rodney L. Johnson

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31 Scopus citations

Abstract

The present study was undertaken to determine if the previously reported in vitro interactions of the Pro-Leu-Gly-NH, (PLG) peptidomimetic analogue 3(R) [(2(S) pyrrolidinylcarbonyl)amino]-2-oxo 1 pyrrolidineacetamide (PAOPA) with the dopaminergic system could be exhibited in an in vivo animal model using 6-hydroxydopamine (6-OHDA)-lesioned rats. In this model, PAOPA was found to potentiate the contralateral rotational behavior induced by either apomorphine or 1 DOPA, PAOPA was 100-fold more potent than PLG, and produced a fourfold greater response than PLG when administered IP. PAOPA also potentiated contralateral rotations induced by SKF-38393 and quinipirole. In summary, the results of this study indicate that PAOPA, a conformationally constrained peptidomimetic analogue of PLG, can modulate dopaminergic activity in vivo with higher potency and efficacy than PLG.

Original languageEnglish (US)
Pages (from-to)1209-1215
Number of pages7
JournalPeptides
Volume18
Issue number8
DOIs
StatePublished - 1997

Keywords

  • 6 OHDA
  • Apomorphine
  • PLG
  • Parkinson's disease
  • Supersensitivity

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