TY - JOUR
T1 - 20-Hydroxyeicosatetraenoic acid (20-HETE)
T2 - Structural determinants for renal vasoconstriction
AU - Yu, Ming
AU - Alonso-Galicia, Magdalena
AU - Sun, Cheng Wen
AU - Roman, Richard J.
AU - Ono, Naoya
AU - Hirano, Hitomi
AU - Ishimoto, Tsuyoshi
AU - Reddy, Y. Krishna
AU - Katipally, Kishta Reddy
AU - Reddy, Komandla Malla
AU - Gopal, V. Raj
AU - Yu, Ji
AU - Takhi, Mohamed
AU - Falck, J R
N1 - Funding Information:
Supported in part by grants from the Robert A. Welch Foundation, Taisho Pharmaceutical Co., Ltd., and NIH grants GM 31278, DK38226, HL29587, HL36279, HL59996.
PY - 2003/7/3
Y1 - 2003/7/3
N2 - 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.
AB - 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.
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U2 - 10.1016/S0968-0896(03)00192-5
DO - 10.1016/S0968-0896(03)00192-5
M3 - Article
C2 - 12788354
AN - SCOPUS:12444336488
SN - 0968-0896
VL - 11
SP - 2803
EP - 2821
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 13
ER -