The GPR18 agonist PSB-KD-107 exerts endothelium-dependent vasorelaxant effects

2021
journal article
article
7
dc.abstract.enGPR18 is an orphan GPCR that is activated by the cannabinoid tetrahydrocannabinol (THC). Emerging evidence indicates its involvement in the control of cardiovascular functions, including heart rate, contractility, vascular tone, as well as blood pressure. Therefore, we investigated the effects of selective GPR18 receptor ligands, namely PSB-KD-107 (agonist) and PSB-CB-92 (antagonist), on blood pressure, electrocardiogram (ECG), and vascular dilatation in vitro and in vivo, as well as their anti-oxidative potential in in vitro ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical (DPPH) assays. Our results clearly show that PSB-KD-107 dilates blood vessels. This effect is related to its activation of GPR18 as it can be blocked by the GPR18 antagonist PSB-CB-92. Moreover, our finding confirms the presence of GPR18 in blood vessels. The mechanism of the vasorelaxant activity of PSB-KD-107 is mainly related to endothelial nitric oxide generation; however, we cannot exclude additional nitric oxide-independent mechanisms or a direct influence on K+ channels. PSB-KD-107 may affect blood pressure and heart function after a single administration; however, this effect was no longer observed after repeated administrations once daily for eight days. PSB-KD-107 does not affect platelet aggregation—an important feature considering the safety of its administration. PSB-KD-107 also shows a significant anti-oxidant effect and further studies of its antioxidant activity in vivo are justified.pl
dc.affiliationWydział Farmaceutyczny : Zakład Technologii i Biotechnologii Środków Leczniczychpl
dc.affiliationWydział Farmaceutyczny : Zakład Biofizyki Farmaceutycznejpl
dc.affiliationWydział Farmaceutyczny : Zakład Farmakokinetyki i Farmacji Fizycznejpl
dc.affiliationWydział Farmaceutyczny : Zakład Wstępnych Badań Farmakologicznychpl
dc.affiliationWydział Farmaceutyczny : Zakład Farmakodynamikipl
dc.cm.id105706
dc.cm.idOmegaUJCMe9c5d9466a324d52a357f8f972cd8e27pl
dc.contributor.authorKotańska, Magdalena - 129276 pl
dc.contributor.authorKubacka, Monika - 130496 pl
dc.contributor.authorBednarski, Marek - 128714 pl
dc.contributor.authorNicosia, Noemipl
dc.contributor.authorSzafarz, Małgorzata - 133549 pl
dc.contributor.authorJawień, Wojciech - 100423 pl
dc.contributor.authorMüller, Christa E.pl
dc.contributor.authorKieć-Kononowicz, Katarzyna - 130088 pl
dc.date.accession2021-12-10pl
dc.date.accessioned2021-12-10T13:24:40Z
dc.date.available2021-12-10T13:24:40Z
dc.date.issued2021pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number8pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume14pl
dc.identifier.articleid799pl
dc.identifier.doi10.3390/ph14080799pl
dc.identifier.eissn1424-8247pl
dc.identifier.issn1424-8247pl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/285023
dc.identifier.weblinkhttps://www.mdpi.com/1424-8247/14/8/799pl
dc.languageengpl
dc.language.containerengpl
dc.pbn.affiliationDziedzina nauk medycznych i nauk o zdrowiu : nauki farmaceutyczne
dc.rightsDodaję tylko opis bibliograficzny*
dc.rights.licenceCC-BY
dc.rights.uri*
dc.share.typeOtwarte czasopismo
dc.subtypeArticlepl
dc.titleThe GPR18 agonist PSB-KD-107 exerts endothelium-dependent vasorelaxant effectspl
dc.title.journalPharmaceuticalspl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
GPR18 is an orphan GPCR that is activated by the cannabinoid tetrahydrocannabinol (THC). Emerging evidence indicates its involvement in the control of cardiovascular functions, including heart rate, contractility, vascular tone, as well as blood pressure. Therefore, we investigated the effects of selective GPR18 receptor ligands, namely PSB-KD-107 (agonist) and PSB-CB-92 (antagonist), on blood pressure, electrocardiogram (ECG), and vascular dilatation in vitro and in vivo, as well as their anti-oxidative potential in in vitro ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical (DPPH) assays. Our results clearly show that PSB-KD-107 dilates blood vessels. This effect is related to its activation of GPR18 as it can be blocked by the GPR18 antagonist PSB-CB-92. Moreover, our finding confirms the presence of GPR18 in blood vessels. The mechanism of the vasorelaxant activity of PSB-KD-107 is mainly related to endothelial nitric oxide generation; however, we cannot exclude additional nitric oxide-independent mechanisms or a direct influence on K+ channels. PSB-KD-107 may affect blood pressure and heart function after a single administration; however, this effect was no longer observed after repeated administrations once daily for eight days. PSB-KD-107 does not affect platelet aggregation—an important feature considering the safety of its administration. PSB-KD-107 also shows a significant anti-oxidant effect and further studies of its antioxidant activity in vivo are justified.
dc.affiliationpl
Wydział Farmaceutyczny : Zakład Technologii i Biotechnologii Środków Leczniczych
dc.affiliationpl
Wydział Farmaceutyczny : Zakład Biofizyki Farmaceutycznej
dc.affiliationpl
Wydział Farmaceutyczny : Zakład Farmakokinetyki i Farmacji Fizycznej
dc.affiliationpl
Wydział Farmaceutyczny : Zakład Wstępnych Badań Farmakologicznych
dc.affiliationpl
Wydział Farmaceutyczny : Zakład Farmakodynamiki
dc.cm.id
105706
dc.cm.idOmegapl
UJCMe9c5d9466a324d52a357f8f972cd8e27
dc.contributor.authorpl
Kotańska, Magdalena - 129276
dc.contributor.authorpl
Kubacka, Monika - 130496
dc.contributor.authorpl
Bednarski, Marek - 128714
dc.contributor.authorpl
Nicosia, Noemi
dc.contributor.authorpl
Szafarz, Małgorzata - 133549
dc.contributor.authorpl
Jawień, Wojciech - 100423
dc.contributor.authorpl
Müller, Christa E.
dc.contributor.authorpl
Kieć-Kononowicz, Katarzyna - 130088
dc.date.accessionpl
2021-12-10
dc.date.accessioned
2021-12-10T13:24:40Z
dc.date.available
2021-12-10T13:24:40Z
dc.date.issuedpl
2021
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
8
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
14
dc.identifier.articleidpl
799
dc.identifier.doipl
10.3390/ph14080799
dc.identifier.eissnpl
1424-8247
dc.identifier.issnpl
1424-8247
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/285023
dc.identifier.weblinkpl
https://www.mdpi.com/1424-8247/14/8/799
dc.languagepl
eng
dc.language.containerpl
eng
dc.pbn.affiliation
Dziedzina nauk medycznych i nauk o zdrowiu : nauki farmaceutyczne
dc.rights*
Dodaję tylko opis bibliograficzny
dc.rights.licence
CC-BY
dc.rights.uri*
dc.share.type
Otwarte czasopismo
dc.subtypepl
Article
dc.titlepl
The GPR18 agonist PSB-KD-107 exerts endothelium-dependent vasorelaxant effects
dc.title.journalpl
Pharmaceuticals
dc.typepl
JournalArticle
dspace.entity.type
Publication

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