New players on the center stage: sphingosine 1-phosphate and its receptors as drug targets

Huwiler, Andrea; Pfeilschifter, Josef (2008). New players on the center stage: sphingosine 1-phosphate and its receptors as drug targets. Biochemical pharmacology, 75(10), pp. 1893-900. New York, N.Y.: Elsevier 10.1016/j.bcp.2007.12.018

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The recent identification of a cellular balance between ceramide and sphingosine 1-phosphate (S1P) as a critical regulator of cell growth and death has stimulated increasing research effort to clarify the role of ceramide and S1P in various diseases associated with dysregulated cell proliferation and apoptosis. S1P acts mainly, but not exclusively, by binding to and activating specific cell surface receptors, the so-called S1P receptors. These receptors belong to the class of G protein-coupled receptors that constitute five subtypes, denoted as S1P(1)-S1P(5), and represent attractive pharmacological targets to interfere with S1P action. Whereas classical receptor antagonists will directly block S1P action, S1P receptor agonists have also proven useful, as recently shown for the sphingolipid-like immunomodulatory substance FTY720. When phosphorylated by sphingosine kinase to yield FTY720 phosphate, it acutely acts as an agonist at S1P receptors, but upon prolonged presence, it displays antagonistic activity by specifically desensitizing the S1P(1) receptor subtype. This commentary will cover the most recent developments in the field of S1P receptor pharmacology and highlights the potential therapeutic benefit that can be expected from these novel drug targets in the future.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Huwiler, Andrea

ISSN:

0006-2952

ISBN:

18321471

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:03

Last Modified:

05 Dec 2022 14:19

Publisher DOI:

10.1016/j.bcp.2007.12.018

PubMed ID:

18321471

Web of Science ID:

000256144600003

URI:

https://boris.unibe.ch/id/eprint/27522 (FactScience: 108719)

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