血小板活化因子受体的研究进展
夏国栋,夏时海, 中国人民武装警察部队医学院附属医院消化内科 天津市 300162
国家自然科学基金资助课题，NO.30300456
项目负责人:夏时海, 300162, 天津市, 中国人民武装警察部队医学院附属医院消化内科. xshhcx@sina.com
电话:022-60578765 传真:022-24370605
收稿日期:2004-10-25 接受日期: 2004-11-12
摘要血小板活化因子(plateletactivating factor，PAF)是目前发现的作用最强的脂质递质，广泛存在各种组织，并通过与其受体结合产生生物学效应.本文就血小板活化因子受体(plateletactivating factor receptor，PAF-R)理化特征、信号传导机制及其拮抗剂的新进展进行了总结与概括，并对其发展进行了展望.
, http://www.100md.com
夏国栋,夏时海. 血小板活化因子受体的研究进展.世界华人消化杂志 2005;13(3):381-384
Sugatani J, Lee DY, Hughes KT, Saito K. Development of a novelscintillation proximity radioimmunoassay for
platelet-activating factormeasurement:comparison with bioassay and GC/MS techniques. Life Sci 1990;46:1443-1450
2 Korth R,Zimmermann K, Richter WO. Lipoprotein-associated paf(LA-paf)was found inwashed human platelets and
, http://www.100md.com
monocyte/macrophage-like U937 cells. ChemPhys Lipids 1994;70:109-119
3 Nakamura M,Honda Z, Izumi T, Sakanaka C, Mutoh H, Minami M, Bito H, Seyama Y,Matsumoto T, Noma M.
Molecular cloning and expression ofplatelet-activating factor receptor from human leukocytes. J Biol Chem
1991;266:20400-20405
4 Kunz D, GerardNP, Gerard C. The human leukocyte platelet-activating factor receptor.cDNA cloning, cell surface
, http://www.100md.com
expression, and construction of a novelepitope-bearing analog. J Biol Chem 1992;267:9101-9106
5 Ye RD,Prossnitz ER, Zou AH, Cochrane CG. Characterization of a human cDNA thatencodes a functional receptor
for platelet activating factor. BiochemBiophys Res Commun 1991;180:105-111
6 Sugimoto T,Tsuchimochi H, McGregor CG, Mutoh H, Shimizu T, Kurachi Y. Molecularcloning and characterization of
, http://www.100md.com
the platelet-activating factor receptorgene expressed in the human heart. Biochem Biophys Res Commun
1992;189:617-624
7 Izumi T,Kishimoto S, Takano T, Nakamura M, Miyabe Y, Nakata M, Sakanaka C, ShimizuT. Expression of human
platelet-activating factor receptor gene inEoL-1 cells following butyrate-induced differentiation. Biochem J
1995;305(Pt 3):829-835
, 百拇医药
8 贺师鹏, 胡雅儿, 夏宗勤. 受体研究技术.第1版. 北京:北京大学医学出版社, 2004:391-392
9 Nakamura M, Honda Z, Izumi T, Sakanaka C, Mutoh H, Minami M, Bito H, Seyama Y, Matsumoto T, Noma M.
Molecular cloning and expression of platelet-activating factor receptor from human leukocytes. J Biol Chem
1991;266:20400-20405
10 Godfroid JJ, Heymans F, Broquet C. Synthesis of ether phospholipids. Pharmacol Res Commun 1986;18(Suppl):1-10
, 百拇医药
11 Nguer CM, Pellegrini O, Galanaud P, Benveniste J, Thomas Y, Richard Y. Regulation of paf-acether receptor expression
in human B cells. J Immunol 1992;149:2742-2748
12 Carmody RJ, Cotter TG. Signaling apoptosis:a radical approach [J]. Redox Report 2001;6:77
13 Hourton D, Stengel D, Chapman MJ, Ninio E. Oxidized low density lipoproteins downregulate LPS-induced
, 百拇医药
platelet-activating factor receptor expression in human monocyte-derived macrophages:implications for LPS-induced
nuclear factor-kappaB binding activity. Eur J Biochem 2001;268:4489-4496
14 Lambrecht G, Parnham MJ. Kadsurenone distinguishes between different platelet activating factor receptor subtypes
on macrophages and polymorphonuclear leucocytes. Br J Pharmacol 1986;87:287-289
, http://www.100md.com
15 Hang W, Diehl JR, Grapes L, Rothschild MF, Roudebush WE. The pig platelet-activating factor receptor gene is
expressed at the mRNA level in different tissues and is mapped to chromosome 6. Anim Reprod Sci 2002;70:277-282
16 Domingo MT, Spinnewyn B, Chabrier PE, Braquet P. Presence of specific binding sites for platelet-activating factor(PAF)
in brain. Biochem Biophys Res Commun 1988;151:730-736
, 百拇医药
17 Homma H, Tokumura A, Hanahan DJ. Binding and internalization of platelet -activating factor 1-O-alkyl-2
-acetyl-sn-glycero-3-phosphocholine in washed rabbit platelets. J Biol Chem 1987;262:10582-10587
18 Shaw JO, Henson PM. The binding of rabbit basophil-derived platelet-activating factor to rabbit platelets.
Am J Pathol 1980;98:791-810
19 Ukena D, Dent G, Birke FW, Robaut C, Sybrecht GW, Barnes PJ. Radioligand binding of antagonists of
, http://www.100md.com
platelet-activating factor to intact human platelets. FEBS Lett 1988;228:285-289
20 Fukunaga K, Ishii S, Asano K, Yokomizo T, Shiomi T, Shimizu T, Yamaguchi K. Single nucleotide polymorphism of
human platelet-activating factor receptor impairs G-protein activation. J Biol Chem 2001;276:43025-43030
21 Chen J, Giri SN. Differences in platelet-activating factor receptor mediated Ca++ response between hamster and
, 百拇医药
guinea pig alveolar macrophages. J Pharmacol Exp Ther 1997;281:1047-1058
22 Centemeri C, Olli S, Tosarello D, Ciceri P, Nicosia S. Heterogeneous platelet-activating factor(PAF)receptors and
calcium increase in platelets and macrophages. Biochem Pharmacol 1999;57:263-271
23 Honda Z, Nakamura M, Miki I, Minami M, Watanabe T, Seyama Y, Okado H, Toh H, Ito K, Miyamoto T. Cloning
, 百拇医药
by functional expression of platelet-activating factor receptor from guinea-pig lung. Nature 1991;349:342-346
24 Izumi T, Kishimoto S, Takano T, Nakamura M, Miyabe Y, Nakata M, Sakanaka C, Shimizu T. Expression of human
platelet-activating factor receptor gene in EoL-1 cells following butyrate-induced differentiation. Biochem J
1995;305(Pt 3):829-835
25 Ishii S, Nagase T, Shimizu T. Platelet-activating factor receptor. Prostaglandins Other Lipid Mediat 2002;68:599-609
, http://www.100md.com
26 Ishii S, Nagase T, Tashiro F, Ikuta K, Sato S, Waga I, Kume K, Miyazaki J, Shimizu T. Bronchial hyperreactivity,increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating
factor receptor. EMBO J 1997;16:133-142
27 Ishii S, Kuwaki T, Nagase T, Maki K, Tashiro F, Sunaga S, Cao WH, Kume K, Fukuchi Y, Ikuta K, Miyazaki J,Kumada M, Shimizu T. Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a
, http://www.100md.com
platelet-activating factor receptor. J Exp Med 1998;187:1779-1788
28 Reeves SR, Zal D. Platelet-activating factor receptor modulates respiratory adaptation to long-term intermittent hypoxia
in mice. Am J Physiol Regul Integr Comp Physiol 2004;287:R369-374
29 Wang X, Sun Z, Borjesson A, Haraldsen P, Aldman M, Deng X, Leveau P, Andersson R. Treatment with lexipafant
, 百拇医药
ameliorates the severity of pancreatic microvascular endothelial barrier dysfunction in rats with acute hemorrhagic
pancreatitis. Int J Pancreatol 1999;25:45-52
30 Rivera JA, Werner J, Warshaw AL, Lewandrowski KB, Rattner DW, Fernandez del Castillo C. Lexipafant fails to improve
survival in severe necrotizing pancreatitis in rats. Int J Pancreatol 1998;23:101-106
, 百拇医药
31 Vincent JL, Spapen H, Bakker J. Phase II multicenter clinical study of the platelet-activating factor receptor antagonist
BB-882 in the treatment of sepsis. Crit Care Med 2000;28:638-642
32 de Souza LJ, Sampietre SN, Assis RS. Effect of platelet-activating factor antagonists(BN-52021, WEB-2170, and BB-882)
on bacterial translocation in acute pancreatitis. J Gastrointest Surg 2001;5:364-370
, http://www.100md.com
33 Marques SA, Dy LC, Southall MD, Yi Q, Smietana E, Kapur R, Marques M, Travers JB, Spandau DF. The
platelet-activating factor receptor activates the extracellular signal-regulated kinase mitogen-activated protein kinase
and induces proliferation of epidermal cells through an epidermal growth factor-receptor-dependent pathway.
J Pharmacol ExpTher 2002;300:1026-1035
, 百拇医药
34 Ikeda O, Egami H, Ishiko T, Ishikawa S, Kamohara H, Hidaka H, Mita S, Ogawa M. Expression of proteinase-activated
receptor-2 in human pancreatic cancer:a possible relation to cancer invasion and induction of fibrosis. Int J Oncol
2003;22:295-300
35 Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM. Platelet-activating factor, a pleiotrophic mediator of
, 百拇医药
physiological and pathological processes. Crit Rev Clin Lab Sci 2003;40:643-672
36 Ishii S, Shimizu T. Platelet-activating factor(PAF)receptor and genetically engineered PAF receptor mutant mice.
Prog Lipid Res 2000;39:41-82
37 Lu DP, Chandrakanthan V, Cahana A, Ishii S, O'Neill C. Trophic signals acting via phosphatidylinositol-3 kinase are
required for normal pre-implantation mouse emlryo development. J Cell Sci 2004;117:1567-1576
, http://www.100md.com
38 Burgos RA, Hidalgo MA, Matthei SM, Hermosilla R, Folch H, Hancke JL. Determination of specific receptor sites for
platelet activating factor in bovine neutrophils. AmJ Vet Res 2004;65:628-636
39 Kafetzis DA, Skevaki C, Costalos C. Neonatal necrotizing enterocolitis:an overview. Curr Opin Infect Dis
2003;16:349-355
40 Serradji N, Bensaid O, Martin M, Kan E, Dereuddre-Bosquet N, Redeuilh C, Huet J, Heymans F, Lamouri A, Clayette P,Dong CZ, Dormont D, Godfroid JJ. Structure-activity relationships in platelet-activating factor(PAF). 10. From PAF
antagonism to inhibition of HIV-1 replication. J Med Chem 2000;43:2149-2154
编辑 张海宁, 百拇医药( 夏国栋, 夏时海)
国家自然科学基金资助课题，NO.30300456
项目负责人:夏时海, 300162, 天津市, 中国人民武装警察部队医学院附属医院消化内科. xshhcx@sina.com
电话:022-60578765 传真:022-24370605
收稿日期:2004-10-25 接受日期: 2004-11-12
摘要血小板活化因子(plateletactivating factor，PAF)是目前发现的作用最强的脂质递质，广泛存在各种组织，并通过与其受体结合产生生物学效应.本文就血小板活化因子受体(plateletactivating factor receptor，PAF-R)理化特征、信号传导机制及其拮抗剂的新进展进行了总结与概括，并对其发展进行了展望.
, http://www.100md.com
夏国栋,夏时海. 血小板活化因子受体的研究进展.世界华人消化杂志 2005;13(3):381-384
Sugatani J, Lee DY, Hughes KT, Saito K. Development of a novelscintillation proximity radioimmunoassay for
platelet-activating factormeasurement:comparison with bioassay and GC/MS techniques. Life Sci 1990;46:1443-1450
2 Korth R,Zimmermann K, Richter WO. Lipoprotein-associated paf(LA-paf)was found inwashed human platelets and
, http://www.100md.com
monocyte/macrophage-like U937 cells. ChemPhys Lipids 1994;70:109-119
3 Nakamura M,Honda Z, Izumi T, Sakanaka C, Mutoh H, Minami M, Bito H, Seyama Y,Matsumoto T, Noma M.
Molecular cloning and expression ofplatelet-activating factor receptor from human leukocytes. J Biol Chem
1991;266:20400-20405
4 Kunz D, GerardNP, Gerard C. The human leukocyte platelet-activating factor receptor.cDNA cloning, cell surface
, http://www.100md.com
expression, and construction of a novelepitope-bearing analog. J Biol Chem 1992;267:9101-9106
5 Ye RD,Prossnitz ER, Zou AH, Cochrane CG. Characterization of a human cDNA thatencodes a functional receptor
for platelet activating factor. BiochemBiophys Res Commun 1991;180:105-111
6 Sugimoto T,Tsuchimochi H, McGregor CG, Mutoh H, Shimizu T, Kurachi Y. Molecularcloning and characterization of
, http://www.100md.com
the platelet-activating factor receptorgene expressed in the human heart. Biochem Biophys Res Commun
1992;189:617-624
7 Izumi T,Kishimoto S, Takano T, Nakamura M, Miyabe Y, Nakata M, Sakanaka C, ShimizuT. Expression of human
platelet-activating factor receptor gene inEoL-1 cells following butyrate-induced differentiation. Biochem J
1995;305(Pt 3):829-835
, 百拇医药
8 贺师鹏, 胡雅儿, 夏宗勤. 受体研究技术.第1版. 北京:北京大学医学出版社, 2004:391-392
9 Nakamura M, Honda Z, Izumi T, Sakanaka C, Mutoh H, Minami M, Bito H, Seyama Y, Matsumoto T, Noma M.
Molecular cloning and expression of platelet-activating factor receptor from human leukocytes. J Biol Chem
1991;266:20400-20405
10 Godfroid JJ, Heymans F, Broquet C. Synthesis of ether phospholipids. Pharmacol Res Commun 1986;18(Suppl):1-10
, 百拇医药
11 Nguer CM, Pellegrini O, Galanaud P, Benveniste J, Thomas Y, Richard Y. Regulation of paf-acether receptor expression
in human B cells. J Immunol 1992;149:2742-2748
12 Carmody RJ, Cotter TG. Signaling apoptosis:a radical approach [J]. Redox Report 2001;6:77
13 Hourton D, Stengel D, Chapman MJ, Ninio E. Oxidized low density lipoproteins downregulate LPS-induced
, 百拇医药
platelet-activating factor receptor expression in human monocyte-derived macrophages:implications for LPS-induced
nuclear factor-kappaB binding activity. Eur J Biochem 2001;268:4489-4496
14 Lambrecht G, Parnham MJ. Kadsurenone distinguishes between different platelet activating factor receptor subtypes
on macrophages and polymorphonuclear leucocytes. Br J Pharmacol 1986;87:287-289
, http://www.100md.com
15 Hang W, Diehl JR, Grapes L, Rothschild MF, Roudebush WE. The pig platelet-activating factor receptor gene is
expressed at the mRNA level in different tissues and is mapped to chromosome 6. Anim Reprod Sci 2002;70:277-282
16 Domingo MT, Spinnewyn B, Chabrier PE, Braquet P. Presence of specific binding sites for platelet-activating factor(PAF)
in brain. Biochem Biophys Res Commun 1988;151:730-736
, 百拇医药
17 Homma H, Tokumura A, Hanahan DJ. Binding and internalization of platelet -activating factor 1-O-alkyl-2
-acetyl-sn-glycero-3-phosphocholine in washed rabbit platelets. J Biol Chem 1987;262:10582-10587
18 Shaw JO, Henson PM. The binding of rabbit basophil-derived platelet-activating factor to rabbit platelets.
Am J Pathol 1980;98:791-810
19 Ukena D, Dent G, Birke FW, Robaut C, Sybrecht GW, Barnes PJ. Radioligand binding of antagonists of
, http://www.100md.com
platelet-activating factor to intact human platelets. FEBS Lett 1988;228:285-289
20 Fukunaga K, Ishii S, Asano K, Yokomizo T, Shiomi T, Shimizu T, Yamaguchi K. Single nucleotide polymorphism of
human platelet-activating factor receptor impairs G-protein activation. J Biol Chem 2001;276:43025-43030
21 Chen J, Giri SN. Differences in platelet-activating factor receptor mediated Ca++ response between hamster and
, 百拇医药
guinea pig alveolar macrophages. J Pharmacol Exp Ther 1997;281:1047-1058
22 Centemeri C, Olli S, Tosarello D, Ciceri P, Nicosia S. Heterogeneous platelet-activating factor(PAF)receptors and
calcium increase in platelets and macrophages. Biochem Pharmacol 1999;57:263-271
23 Honda Z, Nakamura M, Miki I, Minami M, Watanabe T, Seyama Y, Okado H, Toh H, Ito K, Miyamoto T. Cloning
, 百拇医药
by functional expression of platelet-activating factor receptor from guinea-pig lung. Nature 1991;349:342-346
24 Izumi T, Kishimoto S, Takano T, Nakamura M, Miyabe Y, Nakata M, Sakanaka C, Shimizu T. Expression of human
platelet-activating factor receptor gene in EoL-1 cells following butyrate-induced differentiation. Biochem J
1995;305(Pt 3):829-835
25 Ishii S, Nagase T, Shimizu T. Platelet-activating factor receptor. Prostaglandins Other Lipid Mediat 2002;68:599-609
, http://www.100md.com
26 Ishii S, Nagase T, Tashiro F, Ikuta K, Sato S, Waga I, Kume K, Miyazaki J, Shimizu T. Bronchial hyperreactivity,increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating
factor receptor. EMBO J 1997;16:133-142
27 Ishii S, Kuwaki T, Nagase T, Maki K, Tashiro F, Sunaga S, Cao WH, Kume K, Fukuchi Y, Ikuta K, Miyazaki J,Kumada M, Shimizu T. Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a
, http://www.100md.com
platelet-activating factor receptor. J Exp Med 1998;187:1779-1788
28 Reeves SR, Zal D. Platelet-activating factor receptor modulates respiratory adaptation to long-term intermittent hypoxia
in mice. Am J Physiol Regul Integr Comp Physiol 2004;287:R369-374
29 Wang X, Sun Z, Borjesson A, Haraldsen P, Aldman M, Deng X, Leveau P, Andersson R. Treatment with lexipafant
, 百拇医药
ameliorates the severity of pancreatic microvascular endothelial barrier dysfunction in rats with acute hemorrhagic
pancreatitis. Int J Pancreatol 1999;25:45-52
30 Rivera JA, Werner J, Warshaw AL, Lewandrowski KB, Rattner DW, Fernandez del Castillo C. Lexipafant fails to improve
survival in severe necrotizing pancreatitis in rats. Int J Pancreatol 1998;23:101-106
, 百拇医药
31 Vincent JL, Spapen H, Bakker J. Phase II multicenter clinical study of the platelet-activating factor receptor antagonist
BB-882 in the treatment of sepsis. Crit Care Med 2000;28:638-642
32 de Souza LJ, Sampietre SN, Assis RS. Effect of platelet-activating factor antagonists(BN-52021, WEB-2170, and BB-882)
on bacterial translocation in acute pancreatitis. J Gastrointest Surg 2001;5:364-370
, http://www.100md.com
33 Marques SA, Dy LC, Southall MD, Yi Q, Smietana E, Kapur R, Marques M, Travers JB, Spandau DF. The
platelet-activating factor receptor activates the extracellular signal-regulated kinase mitogen-activated protein kinase
and induces proliferation of epidermal cells through an epidermal growth factor-receptor-dependent pathway.
J Pharmacol ExpTher 2002;300:1026-1035
, 百拇医药
34 Ikeda O, Egami H, Ishiko T, Ishikawa S, Kamohara H, Hidaka H, Mita S, Ogawa M. Expression of proteinase-activated
receptor-2 in human pancreatic cancer:a possible relation to cancer invasion and induction of fibrosis. Int J Oncol
2003;22:295-300
35 Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM. Platelet-activating factor, a pleiotrophic mediator of
, 百拇医药
physiological and pathological processes. Crit Rev Clin Lab Sci 2003;40:643-672
36 Ishii S, Shimizu T. Platelet-activating factor(PAF)receptor and genetically engineered PAF receptor mutant mice.
Prog Lipid Res 2000;39:41-82
37 Lu DP, Chandrakanthan V, Cahana A, Ishii S, O'Neill C. Trophic signals acting via phosphatidylinositol-3 kinase are
required for normal pre-implantation mouse emlryo development. J Cell Sci 2004;117:1567-1576
, http://www.100md.com
38 Burgos RA, Hidalgo MA, Matthei SM, Hermosilla R, Folch H, Hancke JL. Determination of specific receptor sites for
platelet activating factor in bovine neutrophils. AmJ Vet Res 2004;65:628-636
39 Kafetzis DA, Skevaki C, Costalos C. Neonatal necrotizing enterocolitis:an overview. Curr Opin Infect Dis
2003;16:349-355
40 Serradji N, Bensaid O, Martin M, Kan E, Dereuddre-Bosquet N, Redeuilh C, Huet J, Heymans F, Lamouri A, Clayette P,Dong CZ, Dormont D, Godfroid JJ. Structure-activity relationships in platelet-activating factor(PAF). 10. From PAF
antagonism to inhibition of HIV-1 replication. J Med Chem 2000;43:2149-2154
编辑 张海宁, 百拇医药( 夏国栋, 夏时海)
