Expression and characterization of Edg-1 receptors in rat cardiomyocytes: Calcium deregulation in response to sphingosine 1-phosphate

Nobuko Nakajima, Amy L. Cavalli, Donatella Biral, Christopher C. Glembotski, Patrick M. McDonough, Peter D. Ho, Romeo Betto, Doriana Sandoná, Philip T. Palade, Christine A. Dettbarn, Robert E. Klepper, Roger A. Sabbadini

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Recent evidence indicates that sphingolipids are produced by the heart during hypoxic stress and by blood platelets during thrombus formation. It is therefore possible that sphingolipids may influence heart cell function by interacting with G-protein-coupled receptors of the Edg family. In the present study, it was found that sphingosine 1-phosphate (Sph1P), the prototypical ligand for Edg receptors, produced calcium overload in rat cardiomyocytes. The cDNA for Edg-1 was cloned from rat cardiomyocytes and, when transfected in an antisense orientation, effectively blocked Edg-1 protein expression and reduced the Sph1P-mediated calcium deregulation. Taken together, these results demonstrate that cardiomyocytes express an extracellular lipid-sensitive receptor-system that can respond to sphingolipid mediators. Because the major source of Sph1P is from blood platelets, we speculate that Edg-mediated Sph1P negative inotropic and cardiotoxic effects may play important roles in acute myocardial ischemia where Sph1P levels are probably elevated in response to thrombus.

Original languageEnglish (US)
Pages (from-to)5679-5686
Number of pages8
JournalEuropean Journal of Biochemistry
Volume267
Issue number18
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Calcium
  • Cardiac
  • Edg
  • G-protein-coupled receptors
  • Sphingosine 1-phosphate

ASJC Scopus subject areas

  • Biochemistry

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