The principle activity of the core will be the preparation of labeled and unlabeled icosanoids, analogues, standards, and inhibitors in sufficient amounts for biological testing, analytical services, and the development of RIAs. Generally all syntheses will be patterned on existing synthetic routes takes from the literature or developed in Dr. Falck's laboratory. Occasionally, it will be necessary to make modifications in the syntheses to accommodate the increased scale of the reactions. Appropriate analytical techniques, e.g., capillary GLC, HPLC and mass nmr spectroscopy, will be applied to intermediate and final products to verify identify and acceptable levels of purity. The core will be responsible for the storage, packing, and distribution of compounds to collaborating program laboratories. Since most icosanoids are available in only minute amounts from natural sources, the resources and services provided by the core facility are essential to the conduct of the program project. The metabolites of the epoxygenase pathway are considered good candidates for initial development of RIAs since they are novel icosanoids with potential relevance to renal function and because they lack a chromophore suitable for UV detection and quantification. RIA will be developed by standard methods utilizing rabbits. The RIAs will be validated by MS techniques.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
Elijovich, Fernando; Milne, Ginger L; Brown, Nancy J et al. (2018) Two Pools of Epoxyeicosatrienoic Acids in Humans: Alterations in Salt-Sensitive Normotensive Subjects. Hypertension 71:346-355
Sausville, Lindsay N; Gangadhariah, Mahesha H; Chiusa, Manuel et al. (2018) The Cytochrome P450 Slow Metabolizers CYP2C9*2 and CYP2C9*3 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production. Cancer Res 78:4865-4877
Garcia, Victor; Gilani, Ankit; Shkolnik, Brian et al. (2017) 20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (Gq) to Affect Vascular Function and Trigger Hypertension. Circ Res 120:1776-1788
Guo, Zhijun; Sevrioukova, Irina F; Denisov, Ilia G et al. (2017) Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria. Cell Chem Biol 24:1259-1275.e6
Zhang, Hui; Falck, John R; Roman, Richard J et al. (2017) Upregulation of 20-HETE Synthetic Cytochrome P450 Isoforms by Oxygen-Glucose Deprivation in Cortical Neurons. Cell Mol Neurobiol 37:1279-1286
Gangadhariah, Mahesha H; Dieckmann, Blake W; Lantier, Louise et al. (2017) Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to insulin sensitivity in mice and in humans. Diabetologia 60:1066-1075
Shuey, Megan M; Billings 4th, Frederic T; Wei, Shouzou et al. (2017) Association of gain-of-function EPHX2 polymorphism Lys55Arg with acute kidney injury following cardiac surgery. PLoS One 12:e0175292
Fan, Fan; Pabbidi, Mallikarjuna R; Ge, Ying et al. (2017) Knockdown of Add3 impairs the myogenic response of renal afferent arterioles and middle cerebral arteries. Am J Physiol Renal Physiol 312:F971-F981
Imig, J D (2016) Epoxyeicosatrienoic Acids and 20-Hydroxyeicosatetraenoic Acid on Endothelial and Vascular Function. Adv Pharmacol 77:105-41
Savas, Üzen; Wei, Shouzou; Hsu, Mei-Hui et al. (2016) 20-Hydroxyeicosatetraenoic Acid (HETE)-dependent Hypertension in Human Cytochrome P450 (CYP) 4A11 Transgenic Mice: NORMALIZATION OF BLOOD PRESSURE BY SODIUM RESTRICTION, HYDROCHLOROTHIAZIDE, OR BLOCKADE OF THE TYPE 1 ANGIOTENSIN II RECEPTOR. J Biol Chem 291:16904-19

Showing the most recent 10 out of 376 publications