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局部麻醉药对人血小板的影响:丝状伪足抑制和内源性蛋白水解

Effects of local anesthetics on human platelets: filopodial suppression and endogenous proteolysis.

作者信息

Nachmias V T, Sullender J S, Fallon J R

出版信息

Blood. 1979 Jan;53(1):63-72.

PMID:758213
Abstract

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 cause platelets to retract filopodia. At short time intervals (up to about 30 min) and low concentrations of the drugs, the filopodia are reextended when the platelets are gel filtered with eluant free of anesthetic. At longer time intervals (1-2 hr) or higher drug concentrations, the retraction becomes irreversible. When the polypeptide composition of the total platelet lysate was examined on SDS gels, proteolysis of two high molecular weight 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. Electron micrographs of platelets lysed on surfaces showed an intermeshed network of filaments to be a major component of the residue. The results suggest that the proteins comprised of these bands may be part of the cytoskeletal system and that their integrity may be necessary for the platelet to reextend filopodia following suppression.

摘要

影响血小板形状的药物可能有助于理解形状变化的机制;因此,局部麻醉药的作用值得进一步研究。局部麻醉药会使血小板的丝状伪足回缩。在短时间间隔(长达约30分钟)和低药物浓度下,当用不含麻醉药的洗脱液对血小板进行凝胶过滤时,丝状伪足会重新伸展。在较长时间间隔(1 - 2小时)或较高药物浓度下,回缩变得不可逆。当在SDS凝胶上检测血小板总裂解物的多肽组成时,当抑制变得不可逆时,可见两条高分子量条带发生蛋白水解。这些多肽估计为250,000和230,000道尔顿,是血小板在低离子强度下裂解时形成的沉淀物的主要成分,并且在通过裂解附着于玻璃珠的血小板并分析附着残留物制成的“细胞骨架”制剂中也富集。在表面裂解的血小板的电子显微镜照片显示,细丝相互交织的网络是残留物的主要成分。结果表明,由这些条带组成的蛋白质可能是细胞骨架系统的一部分,并且它们的完整性对于血小板在抑制后重新伸展丝状伪足可能是必要的。

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