Thrombin receptor activating peptides induce Ca2+ mobilization, barrier dysfunction, prostaglandin synthesis, and platelet-derived growth factor mRNA expression in cultured endothelium

Joe G N Garcia, Carolyn Patterson, Chris Bahler, Judy L. Aschner, C. Michael Hart, Denis English

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Endothelial cell activation by thrombin is a key event in wound healing, inflammation, and hemostasis. To better define thrombin-endothelial cell interactions we synthesized several peptides of varying length corresponding to the initial 14 amino acid sequence of the cloned human platelet thrombin receptor after cleavage at an arginine41 site (R/SFLLRNPNDKYEPF). Thrombin receptor activating peptides (TRAPs) as short as 5 amino acids induced significant levels of PGl2 synthesis and expression of PDGF mRNA in human endothelium and produced dose-dependent cellular contraction and permeability of confluent human umbilical vein and bovine pulmonary artery endothelial monolayers. To explore whether TRAPs utilized similar signal transducing pathways as α-thrombin to accomplish endothelial cell activation, phospholipase C production of the Ca2+ secretagogue IP3 was measured and detected 10 seconds after either TRAP 7 or α-thrombin. Furthermore, TRAPs ranging from 5-14 residues induced significant dose-dependent increases in Fura-2 fluorescence indicative of Ca2+1 mobilization. These results indicate that thrombin-mediated proteolytic cleavage of the human and bovine thrombin receptor initiates stimulus/coupling responses such phospholipase C activation, Ca2+ mobilization, and protein kinase C activation. The functional consequence of this cellular activation via the cleaved receptor is enhanced cellular contraction, barrier dysfunction, PGl2 synthesis, and expression of PDGF mRNA.

Original languageEnglish (US)
Pages (from-to)541-549
Number of pages9
JournalJournal of Cellular Physiology
Volume156
Issue number3
StatePublished - Sep 1993
Externally publishedYes

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Thrombin Receptors
Platelet-Derived Growth Factor
Prostaglandins
Endothelium
Thrombin
Chemical activation
Messenger RNA
Endothelial cells
Endothelial Cells
thrombin receptor peptide (42-55)
Type C Phospholipases
Amino Acids
Umbilical Veins
Fura-2
Platelets
Hemostasis
Cell Communication
Wound Healing
Protein Kinase C
Pulmonary Artery

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Thrombin receptor activating peptides induce Ca2+ mobilization, barrier dysfunction, prostaglandin synthesis, and platelet-derived growth factor mRNA expression in cultured endothelium. / Garcia, Joe G N; Patterson, Carolyn; Bahler, Chris; Aschner, Judy L.; Hart, C. Michael; English, Denis.

In: Journal of Cellular Physiology, Vol. 156, No. 3, 09.1993, p. 541-549.

Research output: Contribution to journalArticle

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