U.S. flagAn official website of the United States government
                    Here's how you know **Official websites use .gov**
                            
                            A **.gov** website belongs to an official government organization in the United States.
 **Secure .gov websites use HTTPS**
                            
                            A **lock** (                            
                              A locked padlock                                                      
                            
                            ) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.


Menu Agricultural Research Service
						
                    U.S. DEPARTMENT OF AGRICULTURE
 Western Human Nutrition Research Center: Davis, CA
 close



    Research

                    Research Projects
                                    Publications
                                    Collaborations
                                    News
                People

                    Staff Listing
                                    Careers


        


                    Laboratories
                        Allen Group
                                    Bennett Group
                                    Stephensen Group
                                    Human Studies
                                    Metabolic Kitchen
                                    Huang Group
                                    Kable Group
                                    Keim Group
                                    Laugero Group
                                    Newman Group
                                    Lemay Group
                                    Support Staff
                    About Us
                        HistorySearch small
                    Search
            
            ARS Home
                                About ARS
                                Contact Us




ARS Home Pacific West Area Davis, California Western Human Nutrition Research Center Research Publications at this Location





- ARS National Programs
- Search for a scientific manuscript
- Search for a research project
- ARS Software
- Programs and Projects
- Collaborations
- Subjects of Investigation
- Publications
- Charles Stephensen
- Charles Stephensen
- Brian Bennett
- Ellen Bonnel
- Yuriko Adkins
- Lindsay Allen
- Bess Caswell
- Liping Huang
- Mary Kable
- Nancy Keim
- Kevin Laugero
- Danielle Lemay
- John Newman
- Ryan Snodgrass
- Zeynep Alkan
- Allyson Deimeke
- Rashel (Shelly) DeCant
- Nicholas Esparza
- Steven Nguyen
- Erik Gertz
- Daniela Hampel
- Shurong Huang
- Xiaowen Jiang
- James Gomez
- Setti Shahab-Ferdows
- Debra Standridge
- Dave Storms

Title:   Author  item
                                            DAVIS, B - UCDMC INTERNAL MED.item
                                            MORISSEAU, C - UCD DEPT. ENTOMOLOGYitem
                                            PEDERSEN, T - UCD DEPT. ENTOMOLOGYitem
                                            Newman, Johnitem
                                            HAMMOCK, B - UCD DEPT. ENTOMOLOGYitem
                                            WEISS, R - UCDMC INTERNAL MED.
  Submitted to: American Society of Pharmacology and Experimental Therapeutics
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 10/11/2005
                                    Publication  Date: 1/1/2006
                                    Citation: Davis, B.B., Morisseau, C., Pedersen, T., Newman, J.W., Hammock, B.D., Weiss, R.H. Attenuation of vascular smooth muscle cell proliferation by 1-cyclohexyl-3-dodecyl urea is independent of soluble epoxide hydrolase inhibition.. American Society of Pharmacology and Experimental Therapeutics. 2006: Vol.316, No.2:815-821.Interpretive Summary: The pharmacological properties of soluble epoxide hydrolase (sEH) inhibitors are being investigated for the treatment of hypertension, atherosclerosis, and inflammatory diseases.  However, the pharmacological targets of these potential drugs have not been fully explored.  This study found that one such sEH inhibitor, 1-cyclohexyl-3-dodecyl urea (CDU), inhibited the growth of multiple vascular cell types independent of an effect on the sEH, while other equally potent inhibitors and the endogenous epoxy fatty acid substrates of the target enzyme did not possess these properties. This study suggests that greasy cyclohexyl-ureas may have useful anti-proliferative properties, and caution against interpretation of biological effects when only found using micromolar concentrations of poorly characterized pharmacological agents.
                                Technical Abstract: Epoxyeicosatrienoic acid(s) (EET) have variable hemodynamic, anti-inflammatory, and growth regulatory effects, and inhibitors of their regulatory enzyme, soluble epoxide hydrolase (sEH), can mimic these effects. For this reason, sEH inhibitors are being studied as potential pharmaceuticals for the treatment of hypertension, atherosclerosis, and inflammatory diseases. We now show that a highly selective urea-based sEH inhibitor 
1-cyclohexyl-3-dodecyl urea (CDU) attenuates human aortic vascular smooth muscle (HVSM) cell proliferation independently of any effect on sEH. CDU also inhibits endothelial cells when stimulated with basic fibroblast growth factor or serum. In addition, we demonstrate that EET, as well as several newer generation sEH inhibitors and a urea-based weak sEH inhibitor, do not affect proliferation in HVSM cells. Structure-activity relationships demonstrate that the addition of an acid group to the dodecyl carbon chain, changing the cyclohexyl group to an adamantyl group, and shortening the carbon chain to two carbons all abolish the antiproliferative effect. Our finding that a highly selective urea-based inhibitor of sEH can alter biology independently of its putative target enzyme suggests that there may be other useful properties of this class of compounds unrelated to their influence on epoxyeicosanoids. In addition, our results show that caution should be used when attempting to infer conclusions of EET biology based solely on the effects these inhibitors in tissue culture models, especially when used at micromolar concentrations.


Return to top


Connect with ARS Sign up


ARS Home
                            USDA.gov
                            Plain Writing
                            Policies & Links
                            Civil Rights Statements
                            FOIA
                            Accessibility Statement
                            Privacy Policy
                            Non-Discrimination Statement
                            Quality of Information
                            USA.gov
                            WhiteHouse.gov