Intraperitoneal administration of 340 kDa human plasma butyrylcholinesterase increases the level of the enzyme in the cerebrospinal fluid of rats.
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 1mg 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.
Sáez-Valero
Javier
J
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, E-03550 Sant Joan d'Alacant, Spain. j.saez@umh.es
de Gracia
José A Pérez
JA
Lockridge
Oksana
O
D000109:Acetylcholine / Q000097:blood / Q000134:cerebrospinal fluid; D000818:Animals; D002091:Butyrylcholinesterase / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D007274:Injections, Intraperitoneal / Q000379:methods; D008297:Male; D008970:Molecular Weight; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002091:Butyrylcholinesterase; D000109:Acetylcholine