Effects of toluene on platelet membrane glycoprotein Ib and actin-binding protein.
Effects of the organic solvent toluene on the platelet membrane receptor glycoprotein Ib (GP Ib) and the cytoskeletal protein, actin-binding protein (ABP), were studied and related to the effects of the local anesthetic dibucaine. The glycocalicin-region of GP Ib contains the binding site for von Willebrand factor; intracellularly GP Ib is linked to the cytoskeleton via ABP. Both GP Ib and ABP are substrates for a calcium-dependent protease, calpain. Washed platelets were incubated with toluene or dibucaine. The toluene concentration in the platelet suspension was analysed by gas chromatography. Using 1.5-2.8 mmol/L toluene, calpain was activated, leading to degradation of ABP and release of glycocalicin from GP Ib. The latter phenomenon was paralleled by a reduced von Willebrand factor-induced platelet agglutination. At lower toluene concentrations (0.3-1.4 mmol/L), degradation of ABP was not detected but an initial increased agglutination that declined to the control level with time was observed. These effects of toluene on the GP Ib-ABP complex are similar to those observed with 1 mmol/L dibucaine. The lowest toluene concentrations used correspond to those that have been found in blood from toluene abusers ("sniffers").
Aakhus
A M
AM
Research Institute for Internal Medicine, Rikshospitalet, University of Oslo, Norway.
Smith-Kielland
A
A
Ripel
A
A
Solum
N O
NO
D015153:Blotting, Western; D003992:Dibucaine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007122:Immunoelectrophoresis; D008840:Microfilament Proteins / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects*; D012967:Sodium Dodecyl Sulfate; D014050:Toluene / Q000494:pharmacology*
D008840:Microfilament Proteins; D010980:Platelet Membrane Glycoproteins; D012967:Sodium Dodecyl Sulfate; D014050:Toluene; D003992:Dibucaine