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LPA3: Pharmacodynamic Differences Between Lysophosphatidic Acid and Oleoyl-Methoxy Glycerophosphothionate: Biased Agonism, Two Sites

Year: 2024
Type: article
Abstract: Lysophosphatidic acid (LPA) and oleoyl-methoxy glycerophosphothionate (OMPT) increased LPA 3 phosphorylation; OMPT being considerably more potent than LPA. OMPT was also more potent than LPA to activate ERK 1/2. In contrast, to increase intracellular calcium OMPT was less effective than LPA. LPA-induced LPA 3 -β-arrestin 2 interaction was fast and robust, whereas that induced by OMPT was only detected at 60 min of incubation. LPA- and OMPT-induced receptor internalization was fast but that of OMPT was more marked. LPA-induced internalization was blocked by Pitstop 2, whereas OMPT-induced receptor internalization was partially inhibited by Pitstop 2 and Filipin and entirely by the combination of both. The data again indicate differences in the actions of these agonists. When LPA-stimulated cells were rechallenged with 1 µM LPA, hardly any response was detected, i.e., a “refractory” state was induced. However, if OMPT was used as the second stimulus, a conspicuous and robust response was observed. These data again suggest the possibility that two binding sites for these agonists might exist in the LPA 3 receptor, one showing a very high affinity for OMPT and another, likely shared by LPA and OMPT (structural analogs) with lower affinity. One sentence summary OMPT, oleoyl-methoxy glycerophosphothionate, a biased agonits interacting with an additional binding site in LPA 3 receptors.
Source: Receptors
DOI: 10.3390/receptors3040029
Language: English
Open Access status: gold
Estimated APC paid: $1,137
OpenAlex ID: W4405640410
FWCI: 0.347
Cites: 42
Cited by: 3
Related to: 10