EFFECTS OF LOCAL-ANESTHETICS ON HUMAN PLATELETS - FILOPODIAL SUPPRESSION AND ENDOGENOUS PROTEOLYSIS

Agents that affect platelet shape may be useful in understanding the mechanism of shape change. For this reason, the effects of local anesthetics are worthy of further study. Local anesthetics caused platelets to retract filopodia. At short time intervals (up to about 30 min) and low concentration of the drugs, the filopodia were reextended when the platelets were gel filtered with eluant free of anesthetic. At longer time intervals (1-2 h) or higher drug concentrations, the retraction became irreversible. When the polypeptide composition of the total platelet lysate was examined on SDS [sodium dodecyl sulfate] gels, proteolysis of 2 high MW bands was seen when the suppression became irreversible. These polypeptides, estimated as 250,000 and 230,000 daltons, were major components of a precipitate that formed when platelets were lysed at low ionic strength and were also enriched in a cytoskeletal preparation made by lysing platelets attached to glass beads and analyzing the adherent residue. EM of platelets lysed on surfaces showed an intermeshed network of filaments to be a major component of the residue. The proteins comprised of these bands may be part of the cytoskeletal system. Their integrity may be necessary for the platelet to reextend filopodia following suppression.