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Whole Blood Assays for Evaluation of Thromboxane Synthase Inhibition

2025-03-27 生物化学 加入收藏
Researchers in the eicosanoid field have frequently applied whole blood assays (

Researchers in the eicosanoid field have frequently applied whole blood assays (1 –3 ) for evaluation of enzymic inhibitors in preclinical and clinical studies. In numerous investigations of antiplatelet agents, the capacity of blood to generate thromboxane A2 (TXA2 ) in response to an agonist has been assessed, and similar assays figure importantly in the current clinical trials (4 ) of cyclooxygenase-2 (COX-2) inhibitors. Early work by Sun (5 ), carried out with human platelet microsomes, established the reaction conditions for studies of thromboxane synthase, and demonstrated that thromboxane synthase is not inhibited by non steroidal anti-inflammatory agents, such as aspirin. It now seems clear that other blood elements, notably monocytes, also contain thromboxane synthase. When the objective is to manipulate, pharmacologically, arachidonic acid (AA) metabolism, or to track routes of transcellular metabolism of AA (discussed in Chapter 16 ), convenient assays are often set up to measure stable products, such as 6-keto-PGF1α and TXB2 ; hydrolysis products of prostacyclin (PGI2 ) and TXA2 , respectively. Depending on the specific purpose, different agonists (e.g., thrombin, collagen, endotoxin) may be used to elicit formation of eicosanoids by blood elements.

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