title: 20-hydroxyeicosatetraenoic acid (20-HETE): structural determinants for renal vasoconstriction.
abstract: 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 delta (Zou et al. Am. J. Physiol. 1996, 270, R228; Gebremedhin, D. et al. Am. J. Physiol. 1998, 507, 771)-, delta (Carroll et al. Am. J. Physiol. 1996, 271, R863; Vazquez et al. Life Sci. 1995, 56, 1455)-, or delta (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 pi-pi binding site in the vicinity of the pi (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 omega-terminus.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Magdalena
authors.initials: M
authors.lastname: Alonso-Galicia
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Sun
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
authors.forename: Naoya
authors.initials: N
authors.lastname: Ono
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hirano
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Y Krishna
authors.initials: YK
authors.lastname: Reddy
authors.forename: Kishta Reddy
authors.initials: KR
authors.lastname: Katipally
authors.forename: Komandla Malla
authors.initials: KM
authors.lastname: Reddy
authors.forename: V Raj
authors.initials: VR
authors.lastname: Gopal
authors.forename: Ji
authors.initials: J
authors.lastname: Yu
authors.forename: Mohamed
authors.initials: M
authors.lastname: Takhi
authors.forename: J R
authors.initials: JR
authors.lastname: Falck
mesh_terms: D000818:Animals; D001665:Binding Sites; D006893:Hydroxyeicosatetraenoic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D018055:Receptors, Eicosanoid / Q000737:chemistry; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D018055:Receptors, Eicosanoid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid