Characterization of a New Peptide Agonist of the Protease-activated Receptor-1

Overview

Journal Biochem Pharmacol

Specialties Biochemistry
Pharmacology

Date 2007 Oct 24

PMID 17950254

Citations 3

Authors

Yingying Mao

Jianguo Jin

Satya P Kunapuli

Affiliations

Soon will be listed here.

Abstract

A new peptide (TFRRRLSRATR), derived from the c-terminal of human platelet P2Y(1) receptor, was synthesized and its biological function was evaluated. This peptide activated platelets in a concentration-dependent manner, causing shape change, aggregation, secretion and calcium mobilization. Of the several receptor antagonists tested, only BMS200261, a protease activated receptor 1 (PAR-1) specific antagonist, totally abolished the peptide-induced platelet aggregation, secretion and calcium mobilization. The TFRRR-peptide-pretreated washed platelets failed to aggregate in response to SFLLRN (10 microM) but not to AYPGKF (500 microM). In addition, in mouse platelets, peptide concentrations up to 600 microM failed to cause platelet activation, indicating that the TFRRR-peptide activated platelets through the PAR-1 receptor, rather than through the PAR-4 receptor. The shape change induced by 10 microM peptide was totally abolished by Y-27632, an inhibitor of p160(ROCK) which is a downstream mediator of G12/13 pathways. The TFRRR-peptide, YFLLRNP, and the physiological agonist thrombin selectively activated G12/13 pathways at low concentrations and began to activate both Gq and G12/13 pathways with increasing concentrations. Similar to SFLLRN, the TFRRR-peptide caused phosphorylation of Akt and Erk in a P2Y(12) receptor-dependent manner, and p-38 MAP kinase activation in a P2Y(12)-independent manner. The effects of this peptide are elicited by the first six amino acids (TFRRRL) whereas the remaining peptide (LSRATR), TFERRN, or TFEERN had no effects on platelets. We conclude that TFRRRL activates human platelets through PAR-1 receptors.

Citing Articles

New PAR1 Agonist Peptide Demonstrates Protective Action in a Mouse Model of Photothrombosis-Induced Brain Ischemia.

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PMID: 32547356 PMC: 7273131. DOI: 10.3389/fnins.2020.00335.

Protease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer.

Sebert M, Sola-Tapias N, Mas E, Barreau F, Ferrand A Front Endocrinol (Lausanne). 2019; 10:717.

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Biased signaling of protease-activated receptors.

Zhao P, Metcalf M, Bunnett N Front Endocrinol (Lausanne). 2014; 5:67.

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