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dc.contributor.authorFrancis, Luc RA
dc.contributor.authorMillington-Burgess, Sarah L
dc.contributor.authorRahman, Taufiq
dc.contributor.authorHarper, Matthew T
dc.date.accessioned2022-01-08T00:30:11Z
dc.date.available2022-01-08T00:30:11Z
dc.date.issued2022-10-03
dc.identifier.issn0953-7104
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332454
dc.description.abstractThrombin is a potent platelet activator, acting through proteinase-activated receptors -1 and -4 (PAR1 and PAR4). Of these, PAR-1 is activated more rapidly and by lower thrombin concentrations. Consequently, PAR-1 has been extensively investigated as a target for anti-platelet drugs to prevent myocardial infarction. Q94 has been reported to act as an allosteric modulator of PAR1, potently and selectively inhibiting PAR1-Gαq coupling in multiple cell lines, but its effects on human platelet activation have not been previously studied. Platelet Ca2+ signaling, integrin αIIbβ3 activation and α-granule secretion were monitored following stimulation by a PAR1-activating peptide (PAR1-AP). Although Q94 inhibited these responses, its potency was low compared to other PAR1 antagonists. In addition, αIIbβ3 activation and α-granule secretion in response to other platelet activators were also inhibited with similar potency. Finally, in endothelial cells, Q94 did not inhibit PAR1-dependent Ca2+ signaling. Our data suggest that Q94 may have PAR1-independent off-target effects in platelets, precluding its use as a selective PAR1 allosteric modulator.
dc.description.sponsorshipBritish Heart Foundation (project grant PG/20/12/34982)
dc.publisherInforma UK Limited
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.titleQ94 is not a selective modulator of proteinase-activated receptor 1 (PAR1) in platelets.
dc.typeArticle
dc.publisher.departmentDepartment of Pharmacology
dc.date.updated2022-01-06T09:18:08Z
prism.publicationNamePlatelets
dc.identifier.doi10.17863/CAM.79900
dcterms.dateAccepted2021-12-24
rioxxterms.versionofrecord10.1080/09537104.2022.2026911
rioxxterms.versionAM
dc.contributor.orcidRahman, Taufiq [0000-0003-3830-5160]
dc.identifier.eissn1369-1635
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBritish Heart Foundation (PG/20/12/34982)
cam.issuedOnline2022-04-13
cam.orpheus.successWed May 25 11:13:10 BST 2022 - Embargo updated
cam.orpheus.counter6
cam.depositDate2022-01-06
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2023-04-13


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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International