Chapter 8. EDRF, an Emerging Target for Drug Design

摘要: Publisher Summary Endothelium-derived relaxing factor (EDRF) has been an important component in the rapidly developing field of vascular biology. Research demonstrated EDRF to be a ubiquitous intra- and intercellular messenger with roles homeostasis, neuronal function, immunological function. More recently number nitrosothiols have suggested as possible EDRFs, including S-nitrosocysteine S-nitrosoproteins. Initial evidence that biochemical conversion L-arginine nitric oxide (NO) or NO-like molecule provided EDRF-like activity endothelial cells. definitive arose from mass spectrometry experiments [15NG]-L-arginine demonstrating incorporation [15N] into NO derived products, nitrate nitrite. Many research groups pursued purification synthase (NOS) various cell tissue sources. Interest mechanism biological oxidation L-citrulline sparked further studies aimed at elucidating this 5 electron process. A phosphorylation sites discovered via sequencing NOS. Protein kinase C calcium calmodulin-dependent protein II reported increase NOS brain The pathway contributes prevention abnormal platelet aggregation, vasoconstriction induced by aggregating platelets ensuing vasospasms. Induction can blocked treatment transforming growth factor-beta, glucocorticoids, some types specific interleukins. peripheral nervous system appears linked nonadrenergic noncholinergic (NANC) pathways involved gastrointestinal Among first therapeutic utilities for inhibitors are sepsis septic shock hypotension associated interleukin therapies. role central (CNS) ischemia therapy is being emerged.