## Abstract The effects of the antimicrotubular drugs colchicine and vinblastine on the blood platelet release reaction were studied by measuring release of ^14^C‐5‐hydroxytryptamine (^14^C‐5‐HT, release I) and β‐glucuronidase (release II) from gel‐filtered human platelets. β‐glucuronidase release
Alteration of thrombine-signaling mechanism by heptachlor in human platelets
✍ Scribed by María G. Moya de Juri; Gladis Magnarelli de Potas; Ana M. Pechen de D'Angelo
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 180 KB
- Volume
- 16
- Category
- Article
- ISSN
- 1095-6670
No coin nor oath required. For personal study only.
✦ Synopsis
Heptachlor is a persistent organochlorine insecticide that has been detected in human tissues and fluids. The ability of heptachlor to interfere with platelet phosphoinositides metabolism and related signaling events stimulated by thrombin was evaluated. In vitro incubations with a concentration range of 1-100 microM heptachlor, prior to platelets activation, were performed. Experiments showed that 10 microM increased protein Kinase C (PKC) activity and phosphatidylinositolbiphosphate and phosphatidic acid phosphorylation. Simultaneously phosphatidylcholine and phosphatidylethanolamine breakdown were prevented. Similar effects were observed with HC 1 microM. However, heptachlor 100 microM increased phosphatidylinositolbiphosphate phosphorylation but reduced serine/threonine kinases activity. We propose that signal transduction steps downstream phospholipase C (PLC) are unphysiologically activated by heptachlor and facilitated by the increase in phosphatidylinositolbiphosphate, the substrate for PLC activity, thus producing an accumulation of phosphatidic acid. The elevated level of this compound itself or the transient increase in diacylglycerol produced may cause calcium mobilization and the activation of PKC. In contrast with the alterations observed in phospholipids and protein phosphorylation, no changes in aggregation properties were observed.
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