A 14 amino acid peptide derived from the amino terminus of the cleaved thrombin receptor elevates intracellular calcium and stimulates prostacyclin production in human endothelial cells.
Cleavage by thrombin of the platelet thrombin receptor exposes a new N-terminal segment SFLLRNPNDKYEPF (SFLL) which acts as a tethered ligand. The free peptide activates platelets and induces platelet aggregation. We now show that SFLL can also activate human umbilical vein endothelial cells (HUVEC) and induce rises in both cytosolic free calcium ([Ca2+]i) and prostacyclin (PGI2) production. These responses were time- and concentration-dependent and were similar to those for native thrombin except that they were not blocked by hirudin. Initial activation of HUVEC with thrombin desensitized the subsequent response to SFLL for both rises in [Ca2+]i and PGI2 production. Thus, SFLL alone can activate HUVEC and elevate [Ca2+]i and induce PGI2 production suggesting that the thrombin receptors on platelet and endothelial cells are functionally and structurally similar.
Ngaiza
J R
JR
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Jaffe
E A
EA
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D018179:Receptors, Thrombin; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology; D014471:Umbilical Veins
D006629:Hirudins; D009842:Oligopeptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; C072032:thrombin receptor peptide (42-55); D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D013917:Thrombin; D002118:Calcium