![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 53, Issue 2, 188-194, February 1998
Departments of
Anesthesiology (C.W.H., M.E.D.),
Chemistry (D.W.H.,
T.L.M.),
Pharmacology (S.P.R., M.E.D., K.R.L.), and
Biochemistry
(S.B.H., K.R.L), University of Virginia, Charlottesville, Virginia
22908
Despite an intriguing cell biology and the suggestion of a role in
pathophysiological responses, the mechanism of action of such lipid
phosphoric acid mediators as lysophosphatidic acid (LPA) remains
obscure, in part because of an underdeveloped medicinal chemistry. We
report now the agonist activity of a synthetic phospholipid in which
the glycerol backbone of LPA is replaced by L-serine. Like
LPA, the L-serine-based lipid mobilizes calcium and
inhibits activation of adenylyl cyclase in the human breast cancer cell line MDA MB231. Treatment with LPA desensitizes MDA MB231 cells to
subsequent application of the L-serine compound; when the
order of application is reversed, however, the L-serine
compound does not prevent calcium mobilization by LPA, which might
indicate the existence of two LPA receptors in these cells. The
analogous D-serine-based phospholipid was distinctly less
potent than the L-isomer in those assays; this finding
demonstrates stereoselectivity by an LPA receptor. Unlike LPA, the
L-serine-based lipid does not evoke a chloride conductance
in Xenopus laevis oocytes, but injection of
poly(A)+ RNA from HEK 293 cells confers this phenotype on
the oocyte. The latter result has practical importance in that it
allows use of the frog oocyte for expression cloning of an LPA receptor
DNA, an assay system made problematic by the oocyte's strong
endogenous response to LPA.
This article has been cited by other articles:
|
|
 |
|
  N. A. Neidlinger, S. K. Larkin, A. Bhagat, G. P. Victorino, and F. A. Kuypers Hydrolysis of Phosphatidylserine-exposing Red Blood Cells by Secretory Phospholipase A2 Generates Lysophosphatidic Acid and Results in Vascular Dysfunction J. Biol. Chem., January 13, 2006; 281(2): 775 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Virag, D. B. Elrod, K. Liliom, V. M. Sardar, A. L. Parrill, K. Yokoyama, G. Durgam, W. Deng, D. D. Miller, and G. Tigyi Fatty Alcohol Phosphates are Subtype-Selective Agonists and Antagonists of Lysophosphatidic Acid Receptors Mol. Pharmacol., May 1, 2003; 63(5): 1032 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hasegawa, J. R. Erickson, G. J. Goddard, S. Yu, S. Liu, K. W. Cheng, A. Eder, K. Bandoh, J. Aoki, R. Jarosz, et al. Identification of a Phosphothionate Analogue of Lysophosphatidic Acid (LPA) as a Selective Agonist of the LPA3 Receptor J. Biol. Chem., March 28, 2003; 278(14): 11962 - 11969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tigyi Selective Ligands for Lysophosphatidic Acid Receptor Subtypes: Gaining Control over the Endothelial Differentiation Gene Family Mol. Pharmacol., December 1, 2001; 60(6): 1161 - 1164. [Full Text] [PDF]
|
|
|
|
|
|
C. E. Heise, W. L. Santos, A. M. Schreihofer, B. H. Heasley, Y. V. Mukhin, T. L. Macdonald, and K. R. Lynch Activity of 2-Substituted Lysophosphatidic Acid (LPA) Analogs at LPA Receptors: Discovery of a LPA1/LPA3 Receptor Antagonist Mol. Pharmacol., December 1, 2001; 60(6): 1173 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Fischer, N. Nusser, T. Virag, K. Yokoyama, D.-a. Wang, D. L. Baker, D. Bautista, A. L. Parrill, and G. Tigyi Short-Chain Phosphatidates Are Subtype-Selective Antagonists of Lysophosphatidic Acid Receptors Mol. Pharmacol., October 1, 2001; 60(4): 776 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. A. Contos, I. Ishii, and J. Chun Lysophosphatidic Acid Receptors Mol. Pharmacol., April 13, 2001; 58(6): 1188 - 1196. [Abstract] [Full Text]
|
|
|
|
|
|
D.-S. Im, C. E. Heise, M. A. Harding, S. R. George, B. F. O'Dowd, D. Theodorescu, and K. R. Lynch Molecular Cloning and Characterization of a Lysophosphatidic Acid Receptor, Edg-7, Expressed in Prostate Mol. Pharmacol., April 1, 2000; 57(4): 753 - 759. [Abstract] [Full Text]
|
|
|
|
|
|
Z. Gao, T. Chen, M. J. Weber, and J. Linden A2B Adenosine and P2Y2 Receptors Stimulate Mitogen-activated Protein Kinase in Human Embryonic Kidney-293 Cells. CROSS-TALK BETWEEN CYCLIC AMP AND PROTEIN KINASE C PATHWAYS J. Biol. Chem., February 26, 1999; 274(9): 5972 - 5980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Fischer, K. Liliom, Z. Guo, N. Nusser, T. Virág, K. Murakami-Murofushi, S. Kobayashi, J. R. Erickson, G. Sun, D. D. Miller, et al. Naturally Occurring Analogs of Lysophosphatidic Acid Elicit Different Cellular Responses through Selective Activation of Multiple Receptor Subtypes Mol. Pharmacol., December 1, 1998; 54(6): 979 - 988. [Abstract] [Full Text]
|
|
|
|
|
|
S. An, T. Bleu, Y. Zheng, and E. J. Goetzl Recombinant Human G Protein-Coupled Lysophosphatidic Acid Receptors Mediate Intracellular Calcium Mobilization Mol. Pharmacol., November 1, 1998; 54(5): 881 - 888. [Abstract] [Full Text]
|
|
|
|
|
|
C. E. Heise, B. F. O'Dowd, D. J. Figueroa, N. Sawyer, T. Nguyen, D.-S. Im, R. Stocco, J. N. Bellefeuille, M. Abramovitz, R. Cheng, et al. Characterization of the Human Cysteinyl Leukotriene 2 Receptor J. Biol. Chem., September 22, 2000; 275(39): 30531 - 30536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Hooks, W. L. Santos, D.-S. Im, C. E. Heise, T. L. Macdonald, and K. R. Lynch Lysophosphatidic Acid-induced Mitogenesis Is Regulated by Lipid Phosphate Phosphatases and Is Edg-receptor Independent J. Biol. Chem., February 9, 2001; 276(7): 4611 - 4621. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
