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 Aschner, C. Michael Hart, Denis English

Research output: Contribution to journalArticle

117 Scopus citations

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 incsreases 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 respones 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, PGI2 synthesis, and expression of PDGF mRNA. © 1993 Wiley‐Liss, Inc.

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

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Thrombin receptor activating peptides induce Ca<sup>2+</sup> mobilization, barrier dysfunction, prostaglandin synthesis, and platelet‐derived growth factor mRNA expression in cultured endothelium'. Together they form a unique fingerprint.

  • Cite this