Binding studies of L-Prolyl-L-leucyl-glycinamide (PLG), a novel antiparkinsonian agent, in normal human brain

Simon Chiu, Yu Wah Wong, James A. Ferris, Rodney L. Johnson, Ram K. Mishra

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

In an attempt to elucidate the mechanism subserving the potential antiparkinsonian properties of L-Prolyl-L-leucyl-glycinamide (PLG) in humans, we used a radioligand binding assay to identify specific binding sites of PLG in normal human brain. 3H-PLG bound to crude membrane homogenates obtained from human striatum with high affinity and in a saturable manner (Bmax = 10.04 ± 0.82 fmoles/mg-1 protein and KD = 3.60 ± 0.43 nM). The regional distribution profile of specific 3H-PLG binding showed that the substantia nigra exhibited the highest level of specific 3H-PLG binding, followed by striatum and hypothalamus. Pharmacologically active analogues of PLG competed for specific 3H-PLG binding with relative potencies correlating with their biological activities in vivo. The results are consistent with the hypothesis that specific PLG binding sites exist in the human brain capable of modulating the sensitivity of dopamine receptors.

Original languageEnglish (US)
Pages (from-to)41-51
Number of pages11
JournalPharmacological Research Communications
Volume15
Issue number1
DOIs
StatePublished - Jan 1983

Bibliographical note

Funding Information:
This study was supported by the Parkinson Foundation of Canada and the Ontario

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