Eicosanoid biosynthesis and action: novel opportunities for pharmacological intervention

Eicosanoid biosynthesis and action: novel opportunities for pharmacological intervention
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类二十烷酸的生物合成和作用:药理学干预的新机会

DOI:
--
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发表时间:
1989
期刊:
The FASEB Journal
影响因子:
--
通讯作者:
C. Patrono
C. Patrono
中科院分区:
--
文献类型:
--
作者:
S. Nicosia;C. Patrono

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新的类花生酸生物合成途径和受体作为潜在的药物干预的目标进行审查。除了花生四烯酸代谢的环氧合酶和脂氧合酶途径外,还在角膜和肾上皮细胞中发现了细胞色素P450依赖性单加氧酶。血栓烷(TX)处置的酶途径的阐明和用于测量尿液代谢物的分析技术的开发使得能够可靠地评估健康和疾病中的TXA 2生物合成,并为在血小板活化的情况下联合使用TX合成酶抑制剂和TXA 2受体拮抗剂提供了理论依据。最近的证据表明,嗜中性粒细胞衍生的白三烯(LT)A4通过其他人类血细胞的跨细胞代谢可能与血小板和中性粒细胞活化血管痉挛现象的发生有关。前列环素(PG 12)、PGE 2、PGD 2、TXA 2/PGH 2和硫肽-LT受体的特征在于分布、信号转导机制和激动剂介导的调节。这些受体的相对选择性激动剂和拮抗剂的开发为几种人类疾病提供了新的治疗策略。尼科西亚,S.;帕特罗诺角类花生酸的生物合成和作用:药理学干预的新机会。FASEB J. 3:1941 - 1948; 1989.
Novel eicosanoid biosynthetic pathways and receptors are reviewed as potential targets for pharmacological intervention. In addition to the cyclooxygenase and lipoxygenase pathways of arachidonate metabolism, a cytochrome P450‐dependent monooxygenase has been identified in corneal and renal epithelial cells. Elucidation of the enzymatic pathways of thromboxane (TX) disposition and development of analytical techniques for measuring urinary metabolites have allowed a reliable assessment of TXA2 biosynthesis in health and disease, and provide a rationale for the combined use of TX‐synthase inhibitors and TXA2‐receptor antagonists in the setting of platelet activation. Recent evidence for a transcellular metabolism of neutrophilderived leukotriene (LT) A4 by other human blood cells might link platelet and neutrophil activation to the occurrence of vasospastic phenomena. Prostacyclin (PG12), PGE2, PGD2, TXA2/PGH2, and sulfidopeptide‐LT receptors are being characterized in terms of distribution, signal‐transduction mechanisms, and agonist‐mediated regulation. Development of relatively selective agonists and antagonists of these receptors is providing novel therapeutic strategies for several human diseases.—Nicosia, S.; Patrono, C. Eicosanoid biosynthesis and action: novel opportunities for pharmacological intervention. FASEB J. 3: 1941‐1948; 1989.
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DOI: --
发表时间: 1986
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影响因子: --
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