Elsevier

Cellular Signalling

Volume 6, Issue 7, September 1994, Pages 743-750
Cellular Signalling

Analogues of the thrombin receptor tetrered-ligand enhance mesangial cell proliferation

https://doi.org/10.1016/0898-6568(94)00043-3Get rights and content

Abstract

Thrombin stimulates cytosolic calcium mobilization and tritiated thymidine incorporation in rat glomerular mesangial cells. This effect may be mwediatyed by a a thrombin recepto similar to the receptor found in human platelets. In order to test this possibility, a series of analogues of the thrombin receptor peptide, SFLL-RNPNDKYEPF, was evaluated for thier effects on mesangial cells. Analogues of the thrombin receptor peptide containing five, six, seven and 14 amino acids were as efficacious as thrombin with resepct to calcium mobilization and thymidine incorporation, although they were significantly less potent. The dissimilarity in potency between thrombin and the thrombin receptor peptides is consistent with the kinetics of the proposed mechanism of action of the enzyme, since the cleavage by thrombin of its receptor results in a tethered ligand which is at a relatively high concentration compared tot he free pepetides in solution. Those thrombin recepto peptide analogues which showed decreased activity in platelets were tested in mesangiall cells. Removal of serine at position one, N-acetylation, or replacement of the phenylalanine at position two with alanine resulted in analogues which were inactive in stimulating mesangial cell prolideration of calcium mobilization. In addition, those analogues which had no stimulatory effects in mesingial cells were not antagonists of SFLLR-mediated calcium mobilization and thymidine incorporation in mesangial cells.

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