白三烯受體

白三烯（LTs）分為羥基酸（如 LTB₄）和半胱氨酰白三烯（如 LTC₄、LTD₄ 和 LTE₄）兩大類。白三烯受體被分為 BLT 和 CysLT 兩種類型，以表示這種基本層級的選擇性，但這兩種類型內也有異質性。因此，BLT 有兩個亞型，稱為 BLT₁ and BLT₂，CysLT 有兩個亞型，稱為 CysLT₁ and CysLT₂。CysLT 受體可能還有進一步的細分，但仍有待證實。LT 受體類型和亞型的分類最初是基於功能資料，使用天然的激動劑和廣泛的拮抗劑。雖然LTB₄ 可被視為BLT受體的選擇性拮抗劑，而半胱氨酰LTs則是CysLT受體的選擇性拮抗劑，但目前尚未有BLT₁ 或任何一種CysLT受體的亞型選擇性拮抗劑的報告。此外，儘管BLT受體和CysLT₁ 受體都有大量的拮抗劑，但尚未有針對CysLT₂ 受體的選擇性拮抗劑的報告。唯一據報導在此受體具有拮抗劑活性的化合物是非選擇性 CysLT 拮抗劑 BAYu9773。CysLT 受體進一步細分的證據是，人和豬肺動脈對半胱氨酰 LTs 的反應對 CysLT₁ and CysLT₂ antagonists 有抵抗力。

BLT₁, BLT₂, CysLT₁ and CysLT₂ receptors have now all been cloned; the first was the human BLT₁ and CysLT₂ antagonists.sub>1 receptor in 1999 from an HL-60 cell cDNA library, and shown to be a G protein-coupled receptor that had been erroneously identified as the P2Y₇ purinoceptor.有趣的是，BLT₁ 受體的啟動子後來被發現位於 BLT₂ 受體基因的開放閱讀框內。CysLT₁ and the CysLT₂ receptors, both cloned in 2000, again proved to be members of the G protein-coupled receptor superfamily.LT受體可能透過G_i 抑制腺苷酸環化酶，以及G_q/11 調節肌醇磷脂水解和鈣調動。

各種使用激發劑、拮抗劑和基因剔除的研究都顯示，LTs 是重要的促發炎媒介，雖然 BLT 和 CysLT 受體所介導的特定作用相當不同。BLT 受體主要介導化學誘導作用；BLT 促效劑能強效招募中性粒細胞，其次是嗜酸性粒細胞到發炎部位。如同其他化學引導劑，例如 fMLP，它們似乎也會誘發溶酶體酵素和超氧離子的釋放。BLT 促效劑似乎對氣道平滑肌沒有直接影響，雖然在豚鼠實驗中，BLT 促效劑可引起氣道平滑肌收縮，但這種效果似乎是繼發於磷脂酶 C 誘導的花生四烯酸從膜磷脂的移動，以及隨後的類前列腺素生成。

胱氨酰LT受體介導一系列其他促發炎作用，例如氣道和血管平滑肌收縮、內皮膜通透性增加，導致血漿滲出和水腫，以及黏稠粘液分泌增加。胱氨酰 LTs 與各種發炎性疾病（尤其是氣喘）有關。一般認為，非類固醇抗發炎劑（環氧化酶抑制劑）在哮喘和發炎性腸道疾病等情況下所產生的不良反應，至少有一部分是因為消除了類促進素誘發的抑制作用，因而增強了 LT 的釋放。强效、长效、口服活性 CysLT 受体阻断药物（如 zafirlukast、montelukast 和 pranlukast）的开发为 CysLT 受体在哮喘中的作用提供了证据；这些化合物现在越来越多地被视为治疗这种疾病的有用药物。有關其他產品的清單，請參閱下面的 "類似產品" 部分。

目前接受的名稱	BLT1	BLT2	CysLT1	CysLT2
None	None	None	None
347 aa (人)
Subtype 選擇性受體激动劑	Not Known 。	12(S)-oxoETE 15(S)-HETE (H1142)	LTD4 (L5011)	BAYu9773 (B9680)
亞類選擇性拮抗劑	U-75302 20-羧基-LTB4 LTB4-氨基丙酰胺 CP-105696	LY-255283	Montelukast (SML0101) Zafirlukast (Z4152) Pranlukast (P0080) Cinalukast (C6239) Pobilukast SKF 104353 LY-170680 BAYx7195 ZD 3523	LTB4 (L0517)	LTB4 (L0517)	LTC	LTC4
Receptor Selective Antagonists<受體選擇性拮抗劑	ZK 158252 CP 195543 RG 14893b SB-209247b SC 53228b ONO 4057b CGS25019Cb RP 69698b LY-293111b	ZK 158252 CP 195543	BAYu9773 (B9680)	BAYu9773a (B9680)
信號轉導機制<	Gi (cAMP modulation)	Gi (cAMP modulation)	Gq/11  (increase IP3/DAG)	Gq/11  (increase IP3/DAG)
Radioligands of Choice<	[3H]-LTD4 [3H]-CGS23131	[H]-LTB4	[3H]-LTD4 [3H]-ICI 198,615	Not Known
白細胞，各種	生理功能	發炎、收縮	發炎	不詳

Footnotes

a) 據報導，BAYu9773 對重組 CysLT₂ 受體具有部分激動劑活性。

 對 BLT₂ 受體的親和力尚未報告。

Abbreviations

BAYu9773： 6(R)-(4′-羧基苯硫基)-5(S)-羥基-7(E),9(E),11(Z),14(Z)-二十碳四烯酸
BAYx7195： (4S)-[4-羧基苯硫基]-7-[4-(4-苯氧基丁氧基)-苯基]-庚-5-(z)-烯酸
CGS23131： 5-(3-羧基苯甲酰基)-2-((6-(4-甲氧基苯基)-5-己烯基)氧基)苯丙酸
CGS25019C： 4-(5-[4-{Aminoiminomethyl}phenoxy]-pentoxy)-3-methoxy-N,N-bis(1-methylethyl)-benzamide-(Z)-2-butenedioate
CP-105696： (+)-1-(3S,4R)-[3-(4-苯基-苄基)-4-羥基-色滿-7-基]環戊烷羧酸
CP-195543：  2-[(3S,4R)-3,4-二氫-4-羥基-3-(苯基甲基)-2H-1-苯並吡喃-7-基]-4-(三氟甲基)苯甲酸
ICI 198,615： [1-[[2-Methoxy-4-[[(phenylsulfonyl)amino]carbonyl]phenyl]methyl]-1H-indazol-6-yl]-carbamic acid cyclopentyl ester
LY-170680 (Sulukast)： 3-(((1R,2E,4Z)-1-((aS)-a-Hydroxy-m-1H-tetrazol-5-ylbenzyl)-2,4-tetradecadienyl)thio)propionic acid
LY-255283： 1-[5-Ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]ethanone
LY-293111: 2-[2-丙基-3-[3-[2-乙基-4-(4-氟苯基)-5-羥基苯氧基]丙氧基]苯氧基]苯甲酸
ONO 4057： 5-[2-(2-Carboxyethyl)-3-[6-(4-Methoxyphenyl)-5E-hexenyl]oxyphenoxy]valeric acid
RG 14893： 4-(2-(Methyl(2-phenethyl)amino)-2-oxoethyl)-8-(phenylmethoxy)-2-naphthalenecarboxylic acid
RP 69698： 2-[[5-Methyl-5-(1H-tetrazol-5-yl)hexyl]oxy]-4,6-diphenylpyridine
SB-209247: (E)-3-[6-[[(2,6-Dichlorophenyl)thio]methyl]-3-(2-phenylethoxy)-2-pyridinyl]-2-propenoic acid
SC 53228： (+)-(S)-7-[3-[2(-Cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl]phenoxy]propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propanoic acid
SKF 104353：  2-羥基-3-羧基乙硫基-3-[2-(8-苯基辛基)苯基]丙酸
U-75302： (5S)-6-[6-[(1E,3R,5Z)-3-Hydroxy-1,5-undecadienyl]-2-pyridinyl]-1,5-hexanediol
ZD 3523: 4-[[5-[((2R)-2- 甲基-4,4,4-三氟丁基)氨基甲酰基]-1-甲基吲哚-3-基]甲基]-3-甲氧基-N-[(2-甲基苯基)磺酰基]苯甲酰胺
ZK 158252： 5-[2-[5-羥基-5-[1-(3-苯基-2-丙炔基)環丁基]-1,3-戊二烯基]環己亞基]-戊酸

類似產品

抱歉，發生意外錯誤。

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參考資料

1. Bäck M, Dahlén S, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE. 2011. International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions. Pharmacol Rev. 63(3):539-584. https://doi.org/10.1124/pr.110.004184

2. Beller TC, Maekawa A, Friend DS, Austen KF, Kanaoka Y. 2004. Targeted Gene Disruption Reveals the Role of the Cysteinyl Leukotriene 2 Receptor in Increased Vascular Permeability and in Bleomycin-induced Pulmonary Fibrosis in Mice. J. Biol. Chem.. 279(44):46129-46134. https://doi.org/10.1074/jbc.m407057200

3. Brink C, Dahlén S, Drazen J, Evans JF, Hay DWP, Nicosia S, Serhan CN, Shimizu T, Yokomizo T. 2003. International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors. Pharmacol Rev. 55(1):195-227. https://doi.org/10.1124/pr.55.1.8

4. Capra V, Ambrosio M, Riccioni G, Rovati G. 2006. Cysteinyl-Leukotriene Receptor Antagonists: Present Situation and Future Opportunities. CMC. 13(26):3213-3226. https://doi.org/10.2174/092986706778742963

5. Heise CE, O'Dowd BF, Figueroa DJ, Sawyer N, Nguyen T, Im D, Stocco R, Bellefeuille JN, Abramovitz M, Cheng R, et al. 2000. Characterization of the Human Cysteinyl Leukotriene 2 Receptor. J. Biol. Chem.. 275(39):30531-30536. https://doi.org/10.1074/jbc.m003490200

6. Kelloway JS. 1997. Zafirlukast: The First Leukotreene-Receptor Antagonist Approved for the Treatment of Asthma. Ann Pharmacother. 31(9):1012-1021. https://doi.org/10.1177/106002809703100912

7. Laidlaw TM, Boyce JA. 2012. Cysteinyl leukotriene receptors, old and new; implications for asthma. Clin Exp Allergy. 42(9):1313-1320. https://doi.org/10.1111/j.1365-2222.2012.03982.x

8. Lynch KR, O'Neill GP, Liu Q, Im D, Sawyer N, Metters KM, Coulombe N, Abramovitz M, Figueroa DJ, Zeng Z, et al. 1999. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature. 399(6738):789-793. https://doi.org/10.1038/21658

9. Massoumi R, Sjölander A. 2007. The Role of Leukotriene Receptor Signaling in Inflammation and Cancer. The Scientific World JOURNAL. 71413-1421. https://doi.org/10.1100/tsw.2007.200

10. Metters KM. 1995. Leukotriene receptors. Journal of Lipid Mediators and Cell Signalling. 12(2-3):413-427. https://doi.org/10.1016/0929-7855(95)00027-n

11. Fretland DJ, Penning TD. 1996. Overview Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis Recent advances in leukotriene B4 receptor antagonist research. Expert Opinion on Therapeutic Patents. 6(1):21-28. https://doi.org/10.1517/13543776.6.1.21

12. Shirasaki H. 2008. Cysteinyl leukotriene receptor CysLT1as a novel therapeutic target for allergic rhinitis treatment. Expert Opinion on Therapeutic Targets. 12(4):415-423. https://doi.org/10.1517/14728222.12.4.415

13. Tager AM, Bromley SK, Medoff BD, Islam SA, Bercury SD, Friedrich EB, Carafone AD, Gerszten RE, Luster AD. 2003. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol. 4(10):982-990. https://doi.org/10.1038/ni970

14. Tudhope SR, Cuthbert NJ, Abram TS, Jennings MA, Maxey RJ, Thompson AM, Norman P, Gardiner PJ. 1994. BAY u9773, a novel antagonist of cysteinyl-leukotrienes with activity against two receptor subtypes. European Journal of Pharmacology. 264(3):317-323. https://doi.org/10.1016/0014-2999(94)00485-4

15. Walch L, Norel X, Bäck M, Gascard J, Dahlén S, Brink C. 2002. Pharmacological evidence for a novel cysteinyl-leukotriene receptor subtype in human pulmonary artery smooth muscle. 137(8):1339-1345. https://doi.org/10.1038/sj.bjp.0704991

16. Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T. 1997. A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature. 387(6633):620-624. https://doi.org/10.1038/42506

17. Yokomizo T, Kato K, Hagiya H, Izumi T, Shimizu T. 2001. Hydroxyeicosanoids Bind to and Activate the Low Affinity Leukotriene B4 Receptor, BLT2. J. Biol. Chem.. 276(15):12454-12459. https://doi.org/10.1074/jbc.m011361200