Encapsulation of phosphotriesterase within murine erythrocytes.
A new conceptual approach was employed to antagonize organophosphorus intoxication by using resealed carrier erythrocytes containing a recombinant phosphotriesterase. This enzyme has been reported to hydrolyze many organophosphorus compounds, including paraoxon, a potent cholinesterase inhibitor. Paraoxon is rapidly hydrolyzed by this enzyme to p-nitrophenol and diethylphosphate. Incorporation of phosphotriesterase within resealed murine erythrocytes was accomplished by hypotonic dialysis. The properties of this enzyme within these resealed erythrocytes were investigated. Addition of paraoxon to reaction mixtures containing these resealed erythrocytes loaded with phosphotriesterase resulted in the rapid hydrolysis of paraoxon. Hydrolysis of paraoxon did not occur when these carrier erythrocytes contained no phosphotriesterase. These in vitro studies suggest that carrier erythrocytes may be developed as an approach for the prophylactic and therapeutic antagonism of organophosphorus intoxication.
Pei
L
L
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University Health Science Center, College Station 77843-1114.
Omburo
G
G
McGuinn
W D
WD
Petrikovics
I
I
Dave
K
K
Raushel
F M
FM
Wild
J R
JR
DeLoach
J R
JR
Way
J L
JL
D000818:Animals; D043303:Aryldialkylphosphatase; D004337:Drug Carriers; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism; D004950:Esterases / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006868:Hydrolysis; D051379:Mice; D010261:Paraoxon / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004337:Drug Carriers; D004950:Esterases; D043303:Aryldialkylphosphatase; D010261:Paraoxon