Selective ligands for lysophosphatidic acid receptor subtypes: gaining control over the endothelial differentiation gene family.
Selective ligands for lysophosphatidic acid receptor subtypes: gaining control over the endothelial differentiation gene family.
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溶血磷脂酸受体亚型的选择性配体：获得对内皮分化基因家族的控制。
DOI：
10.1124/mol.60.6.1161
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发表时间：
2001
影响因子：
3.6
通讯作者：
Tigyi,G
中科院分区：
文献类型：
--
作者：
Tigyi,G
In this issue of Molecular Pharmacology, Heise et al.(2001) report their results with derivatives of N-acyl ethanolamide phosphate that display subtype-selective agonist and antagonist properties for the endothelial differentiation gene (EDG) family of lysophosphatidic acid (LPA) receptors (Heise et al., 2001). This report follows a publication by Fischer et al.(2001) in the October issue of Molecular Pharmacology reporting on the LPA receptor subtype-selective antagonist properties of short-chain phosphatidic acids. These compounds might be the prototypes of tools long awaited by researchers attempting to unravel the physiological and pathophysiological roles of growth factor-like phospholipids. Lysophosphatidic acid (1-acyl-2-sn-glycero-3-phosphate) and sphingosine-1-phosphate (S1P) have generated considerable interest among cell biologists and pharmacologists since the early 1990s because of their ability to evoke robust Ca2 responses and changes in cell shape at nanomolar concentrations (for review, see Moolenaar, 1999; Pyne and Pyne, 2000; Tigyi, 2001). This interest has been augmented by the ability of LPA and S1P to elicit mitogenic responses and to sustain the survival of cultured cells at micromolar concentrations. The biological effects of these lipids are utilized—unwittingly by most—when serum, which contains LPA in the 10 μM range (Baker et al., 2001) and S1P in the 100 nM range (Yatomi et al., 1995), is added to culture media. The biological responses to LPA and S1P are consistent with those of ligands acting through specific G protein-coupled receptors. However, because of the hydrophobic nature of these ligands, the application of radioligand binding assays for the detection of specific receptors has been challenging. This is one of the factors that have made the molecular cloning of the phospholipid growth factor receptors difficult. However, Hecht et al.(1996) identified LPA as a ligand for a G-proteincoupled receptor they isolated from the ventricular zone of the developing mouse brain. The cloned and overexpressed vzg-1 gene mediated serum-induced retraction of neurites in cortical neurons, a characteristic response elicited by LPA application in PC12 (Tigyi and Miledi 1992) and N1E115 (Jalink et al., 1993) neuroblastoma cells noted earlier. Vzg-1 was later named EDG2 (Contos et al., 2000) because it was shown to be highly homologous to a family of G-proteincoupled orphan receptors. The first member of this family was cloned by Hla and Maciag as a phorbol ester-induced early response gene in vascular endothelial cells (Hla and Maciag 1990); hence, it was named EDG1 for endothelial differentiation gene-1. In 1998, Lee et al. reported that S1P was an endogenous ligand for EDG-1. After this report, several groups have identified other members of this family, including the genes for the LPA-specific EDG4 (An et al., 1998) and EDG7 (Aoki et al., 2000) receptors and the S1P-specific EDG3/5 (An et al., 1997), EDG-6 (Gräler et al., 1998), and EDG8 receptors (Im et al., 2000). This year, the IUPHAR Nomenclature Committee proposed a new nomenclature, based on the receptor’s natural ligand and the chronological order of its discovery, to replace the colloquial EDG terminology (Table 1).Fischer et al.(1998) have shown that most cell types coexpress multiple subtypes of the EDG family receptors. Moreover, there are hints that the EDG family might not represent the only receptors for LPA and S1P (Guo et al., 1996; Hooks et al., 2001). The complexity of the pharmacology of these receptors has delayed the identification of ligands with receptor-selective antagonist and agonist properties. Such compounds are essential …
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影响因子：
3.6
作者：
Heise, CE;Santos, WL;Lynch, KR
通讯作者：
Lynch, KR
DOI：
10.1016/s0006-291x(82)80113-7
发表时间：
1982-01-01
影响因子：
3.1
作者：
SIMON, MF;CHAP, H;DOUSTEBLAZY, L
通讯作者：
DOUSTEBLAZY, L
影响因子：
2.9
作者：
Baker, DL;Desiderio, DM;Tigyi, GJ
通讯作者：
Tigyi, GJ
DOI：
--
发表时间：
1999-10
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Cristina L. Rizza;N. Leitinger;Junming Yue;D. J. Fischer;De-an Wang;P. T. Shih;Helen H. Lee;G. Tigyi;J. Berliner
通讯作者：
Cristina L. Rizza;N. Leitinger;Junming Yue;D. J. Fischer;De-an Wang;P. T. Shih;Helen H. Lee;G. Tigyi;J. Berliner
DOI：
10.1016/s0021-9258(19)36618-9
发表时间：
1992-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Gabor Tigyi;Ricardo Miledi
通讯作者：
Gabor Tigyi;Ricardo Miledi