Short-Chain Phosphatidates Are Subtype-Selective Antagonists of Lysophosphatidic Acid Receptors

Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are members of the phospholipid growth factor family. A major limitation in the field to date has been a lack of receptor subtype-specific agonists and antagonists. Here, we report that dioctylglycerol pyrophosphate and dioctylphosphatidi...

Full description

Saved in:
Bibliographic Details
Published in:Molecular pharmacology 2001-10, Vol.60 (4), p.776-784
Main Authors: Fischer, D J, Nusser, N, Virag, T, Yokoyama, K, Wang Da, Baker, D L, Bautista, D, Parrill, A L, Tigyi, G
Format: Article
Language:English
Subjects:
3T3 Cells
Acetylcholine - metabolism
Adenosine Triphosphate - metabolism
Animals
Binding, Competitive
Calcium - metabolism
Cell Division - drug effects
Cell Line
Diphosphates - pharmacology
Glycerol - analogs & derivatives
Glycerol - pharmacology
Mice
Oocytes - drug effects
Oocytes - metabolism
PC12 Cells
Rats
Receptors, Cell Surface - antagonists & inhibitors
Receptors, Cell Surface - metabolism
Receptors, G-Protein-Coupled
Receptors, Lysophosphatidic Acid
Receptors, Lysophospholipid
Serotonin - metabolism
Thrombin - metabolism
Xenopus laevis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are members of the phospholipid growth factor family. A major limitation in the field to date has been a lack of receptor subtype-specific agonists and antagonists. Here, we report that dioctylglycerol pyrophosphate and dioctylphosphatidic acid are selective antagonists of the LPA 1 and LPA 3 receptors, but prefer LPA 3 by an order of magnitude. Neither molecule had an agonistic or antagonistic effect on LPA 2 receptor. Consistent with this receptor subtype selectivity, dioctylglycerol pyrophosphate inhibited cellular responses to LPA in NIH3T3 fibroblasts, HEY ovarian cancer cells, PC12 pheochromocytoma cells, and Xenopus laevis oocytes. Responses elicited by S1P in these cell lines that endogenously express S1P 1 , S1P 2 , S1P 3 , and S1P 5 receptors were unaffected by dioctylglycerol pyrophosphate. Responses evoked by the G protein-coupled receptor ligands acetylcholine, serotonin, ATP, and thrombin receptor-activating peptide were similarly unaffected, suggesting that the short-chain phosphatidates are receptor subtype-specific lysophosphatidate antagonists.
ISSN:0026-895X
1521-0111