1.Brazilin isolated from Caesalpinia sappan L. acts as a novel collagen receptor agonist in human platelets.
Chang Y1, Huang SK, Lu WJ, Chung CL, Chen WL, Lu SH, Lin KH, Sheu JR. J Biomed Sci. 2013 Jan 25;20:4. doi: 10.1186/1423-0127-20-4.
BACKGROUND: Brazilin, isolated from the heartwood of Caesalpinia sappan L., has been shown to possess multiple pharmacological properties.
2.Blockade of proteinase-activated receptor 4 inhibits neutrophil recruitment in experimental inflammation in mice.
Gomides LF1, Lima OC, Matos NA, Freitas KM, Francischi JN, Tavares JC, Klein A. Inflamm Res. 2014 Nov;63(11):935-41. doi: 10.1007/s00011-014-0767-8. Epub 2014 Aug 14.
OBJECTIVE AND DESIGN: The activation of proteinase-activated receptors (PARs) has been implicated in the development of important hallmarks of inflammation, including in vivo leukocyte recruitment; however, its role in the regulation of leukocyte migration in response to inflammatory stimuli has not been elucidated until now. Here, we examined the effects of the PAR4 antagonist YPGKF-NH 2 (tcY-NH2) on neutrophil recruitment in experimentally induced inflammation.
3.Proteinase-activated receptor 4 (PAR4): activation and inhibition of rat platelet aggregation by PAR4-derived peptides.
Hollenberg MD1, Saifeddine M. Can J Physiol Pharmacol. 2001 May;79(5):439-42.
We studied the actions of receptor-activating peptide analogues (PAR4APs), modeled on the proteolytically-revealed tethered ligand sequence of murine proteinase-activated receptor-4 (PAR4), in a rat platelet aggregation assay. The PAR4APs GYPGKF-NH2 (GY-NH2) and AYPGKF-NH2 (AY-NH2) were able to cause aggregation with EC50 values of about 40 microM and 15 microM, respectively. The reverse human PAR4 sequence (VQGPYG-NH2, YG-NH2) and the PAR1AP SFLLR-NH2, did not cause aggregation. In contrast, trans-cinnamoyl-YPGKF-NH2 (tcY-NH2) did not cause aggregation but blocked aggregation caused by GY-NH2, AY-NH2, and thrombin without affecting ADP-mediated aggregation. We conclude that in contrast to the PAR1AP, the PAR4APs GY-NH2 and AY-NH2 activate rat platelets via a PAR4-related receptor and that peptide analogues modeled on the PAR4 tethered activating sequence can serve as useful agonist and antagonist probes for assessing the consequence of activating PAR4 either by PAR4APs or thrombin in rat tissue preparations.
4.Differential involvement of thrombin receptors in Ca2+ release from two different intracellular stores in human platelets.
Jardin I1, Ben Amor N, Bartegi A, Pariente JA, Salido GM, Rosado JA. Biochem J. 2007 Jan 1;401(1):167-74.
Physiological agonists increase cytosolic free Ca2+ concentration to regulate a number of cellular processes. The platelet thrombin receptors, PAR (protease-activated receptor) 1 PAR-4 and GPIb-IX-V (glycoprotein Ib-IX-V) have been described as potential contributors of thrombin-induced platelet aggregation. Platelets present two separate Ca2+ stores, the DTS (dense tubular system) and acidic organelles, differentiated by the distinct sensitivity of their respective SERCAs (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPases) to TG (thapsigargin) and TBHQ [2,5-di-(tert-butyl)-1,4-hydroquinone]. However, the involvement of the thrombin receptors in Ca2+ release from each Ca2+ store remains unknown. Depletion of the DTS using ADP, which releases Ca2+ solely from the DTS, in combination with 10 nM TG, to selectively inhibit SERCA2 located on the DTS reduced Ca2+ release evoked by the PAR-1 agonist, SFLLRN, and the PAR-4 agonist, AYPGKF, by 80 and 50% respectively.
