20-Hydroxyeicosatetraenoic acid (20-HETE): Structural determinants for renal vasoconstriction

Ming Yu, Magdalena Alonso-Galicia, Cheng Wen Sun, Richard J. Roman, Naoya Ono, Hitomi Hirano, Tsuyoshi Ishimoto, Y. Krishna Reddy, Kishta Reddy Katipally, Komandla Malla Reddy, V. Raj Gopal, Ji Yu, Mohamed Takhi, J R Falck

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The effects of natural and synthetic eicosanoids on the diameter of rat interlobular arteries studied in vitro were compared to that of the potent, endogenous vasoconstrictor 20-HETE. Vasoconstrictor activity was optimum for chain lengths of 20-22 carbons with at least one olefin or epoxide between located between C(13)-C(15) and an oxygen substituent at C(20)-C(22). The presence of Δ (Zou et al. Am. J. Physiol. 1996, 270, R228; Gebremedhin, D. et al. Am. J. Physiol. 1998, 507, 771)-, Δ (Carroll et al. Am. J. Physiol. 1996, 271, R863; Vazquez et al. Life Sci. 1995, 56, 1455)-, or Δ (Imig et al. Hypertension 2000, 35, 307; Lopez et al. Amer. J. Physiol. 2001, 281, F420)-olefins had no influence on the vasoconstrictor response whereas the introduction of a C(7)-thiomethylene enhanced potency. A sulfonamide or alcohol, but not a lactone, could replace the C(1)-carboxylate. These data were used to construct a putative binding domain map of the 20-HETE receptor consisting of: (i) a comparatively open, hydrophilic binding site accommodating the C(1)-functionality; (ii) a hydrophobic trough spanning the olefins; (iii) a shallow pocket containing a critical π-π binding site in the vicinity of the π (Ito et al. Am. J. Physiol. 1998, 274, F395; Quigley, R.; Baum, M.; Reddy, K. M.; Griener, J. C.; Falck, J. R. Am. J. Physiol. 2000, 278, F949)-olefin; and (iv) an oxyphilic binding site proximate to the ω-terminus.

Original languageEnglish (US)
Pages (from-to)2803-2821
Number of pages19
JournalBioorganic and Medicinal Chemistry
Issue number13
StatePublished - Jul 3 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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