Intraperitoneal administration of 340 kDa human plasma butyrylcholinesterase increases the level of the enzyme in the cerebrospinal fluid of rats

Javier Sáez-Valero, José A. Pérez De Gracia, Oksana Lockridge

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Human butyrylcholinesterase (BuChE) is being developed as a new therapeutic for protection against the toxicity of organophosphorus agents and cocaine. The purified BuChE consists predominantly of 340 kDa tetramers and contains less than 5% monomers and dimers. Our goal was to determine whether BuChE crosses the blood-cerebrospinal fluid (CSF) barrier. Rats were injected intraperitoneally with 1 mg of purified human BuChE. Plasma BuChE activity increased nearly 400-fold, while BuChE activity in the CSF increased three-fold. Sucrose density centrifugation showed that the human BuChE molecule in the rat CSF was a tetramer. Immunoprecipitation confirmed the identity of the CSF BuChE as human BuChE. The lower amount of human BuChE in the CSF (0.04%) than of smaller proteins (0.1-1%), with respect to their levels in plasma, supports the idea that passage through the blood-CSF barrier depends on molecular size. BuChE in the CSF could serve to protect the brain from the neurotoxicity of organophosphorus pesticides and cocaine.

Original languageEnglish (US)
Pages (from-to)93-98
Number of pages6
JournalNeuroscience Letters
Volume383
Issue number1-2
DOIs
StatePublished - Jul 22 2005

Keywords

  • Butyrylcholinesterase
  • Cerebrospinal fluid
  • Neurotoxicity
  • Organophosphorus

ASJC Scopus subject areas

  • Neuroscience(all)

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