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Endothelin-elicited stimulation of phospholipase C is mediated by guanine nucleotide binding protein(s).

Abstract
In permeabilized C6 glioma cells and NIH 3T3 cells, the peptide endothelin 1 (ET-1) in combination with GTP gamma S stimulates the formation of inositol phosphates. In the presence of 10 microM GTP gamma S, ET-1 induces the formation of inositol phosphates with an EC50 value of 2.5 nM for C6 glioma cells and 1.6 nM for NIH 3T3 cells. The analogous peptide endothelin 3 (ET-3) is less potent than ET-1 in such action. In NIH 3T3 cells, ET-1+GTP gamma S-induced formation of inositol phosphates could be detected after 1 min of stimulation, and it increased for up to 30 min. ET-1-induced effects were partially reduced by pretreatment of the cells with pertussis toxin (1 microgram/ml) in C6 glioma cells, but were unaffected in NIH 3T3 cells. In binding studies in whole C6 cells and NIH 3T3 cells, specific binding for [125I]ET-1 was detected. Cross-linking of [125I]ET-1 in whole C6 cells revealed the presence of two binding proteins for ET-1 of 74 kDa and 55 kDa. ET-1 at 100 nM inhibited the labeling of both proteins by [125I]ET-1. However, ET-3 inhibited the labeling of the 55 kDa protein only. The results provide direct evidence for endothelin receptor coupling to phospholipase C through guanine nucleotide binding (G) proteins. In addition, in C6 cells, endothelin-mediated phospholipase C activation is partially inhibited by pertussis toxin pretreatment. The endothelin receptor involved in phospholipase C stimulation in C6 cells seems to correspond to a 74 kDa protein which binds ET-1 but not ET-3.
AuthorsF Gusovsky
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 225 Issue 4 Pg. 339-45 (Apr 10 1992) ISSN: 0014-2999 [Print] Netherlands
PMID1323477 (Publication Type: Journal Article)
Chemical References
  • Cross-Linking Reagents
  • Endothelins
  • Inositol Phosphates
  • Receptors, Cell Surface
  • Receptors, Endothelin
  • Virulence Factors, Bordetella
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Pertussis Toxin
  • Type C Phospholipases
  • GTP-Binding Proteins
Topics
  • 3T3 Cells
  • Animals
  • Cross-Linking Reagents
  • Endothelins (pharmacology)
  • GTP-Binding Proteins (metabolism)
  • Glioma
  • Guanosine 5'-O-(3-Thiotriphosphate) (pharmacology)
  • Inositol Phosphates (metabolism)
  • Mice
  • Pertussis Toxin
  • Receptors, Cell Surface (metabolism)
  • Receptors, Endothelin
  • Tumor Cells, Cultured
  • Type C Phospholipases (metabolism)
  • Virulence Factors, Bordetella (pharmacology)

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