In vitro binding of oxime acetylcholinesterase reactivators to proteoglycans synthesized by cultured chondrocytes and fibroblasts.
The incorporation of the 14C-labelled acetylcholinesterase reactivators 1-(methyl-imidazolium)-3 (4-carbaldoxime-pyridinium) propane dibromide (pyrimidoxime) and N,N'-trimethylene bis(pyridinium-4-aldoxime) dibromide (TMB4) into cultured chondrocytes and fibroblasts was measured and their binding to macromolecules synthesized by these cells studied. The results showed that these drugs concentrated slowly and poorly into these cells, but bound firmly to high molecular mass materials in the culture supernatants. The chromatographic properties of these macromolecules on Sepharose CL-2B in non-dissociative or dissociative conditions were similar to those of the proteoglycans synthesized by these cells. Dialysis of the macromolecule-bound drugs against increasing pH buffers showed half-dissociation pH > 8, identical to those for chondroitin sulphate. These results suggest strongly that pyrimidoxime and TMB4 are bound to proteoglycans by ionic interactions, and this together with their poor lipophilicity can explain their high selectivity for the cartilaginous tissues as opposed to other proteoglycan-containing structures such as skin.
Maurizis
J C
JC
INSERM U71, Clermont-Ferrand, France.
Ollier
M
M
Nicolas
C
C
Madelmont
J C
JC
Garrigue
H
H
Veyre
A
A
D000818:Animals; D002250:Carbon Radioisotopes; D002356:Cartilage / Q000378:metabolism; D002478:Cells, Cultured; D002801:Cholinesterase Reactivators / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism*; D046911:Macromolecular Substances; D010091:Oximes / Q000378:metabolism*; D011220:Pralidoxime Compounds / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits; D012867:Skin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013462:Sulfur Radioisotopes; D014289:Trimedoxime / Q000378:metabolism*
D002250:Carbon Radioisotopes; D002801:Cholinesterase Reactivators; D007093:Imidazoles; D046911:Macromolecular Substances; D010091:Oximes; D011220:Pralidoxime Compounds; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; D014289:Trimedoxime