The GPR18 Agonist PSB-KD-107 Exerts Endothelium-Dependent Vasorelaxant Effects.
GPCR
GPR18
agonist
cannabinoid
orphan receptor
vasodilation
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
13 Aug 2021
13 Aug 2021
Historique:
received:
30
06
2021
revised:
04
08
2021
accepted:
10
08
2021
entrez:
28
8
2021
pubmed:
29
8
2021
medline:
29
8
2021
Statut:
epublish
Résumé
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
Identifiants
pubmed: 34451896
pii: ph14080799
doi: 10.3390/ph14080799
pmc: PMC8398562
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Uniwersytet Jagielloński Collegium Medicum
ID : N42/DBS/000045, N42/DBS/000138, N42/DBS/000039, N42/DBS/000139
Références
PeerJ. 2016 Mar 21;4:e1835
pubmed: 27018161
J Endocrinol Invest. 2018 May;41(5):609-619
pubmed: 29110282
PLoS One. 2013 Apr 24;8(4):e61462
pubmed: 23637839
J Pharmacol Exp Ther. 2005 Aug;314(2):780-8
pubmed: 15878999
Psychopharmacology (Berl). 2014 Aug;231(15):3009-17
pubmed: 24577515
Molecules. 2021 Apr 15;26(8):
pubmed: 33921144
Glia. 2012 Jul;60(7):1182-90
pubmed: 22535572
Mol Med Rep. 2016 Oct;14(4):2899-903
pubmed: 27484193
Methods Enzymol. 1999;299:15-27
pubmed: 9916193
Eur J Med Chem. 2018 Jul 15;155:381-397
pubmed: 29902723
Eur J Pharmacol. 2017 Jan 5;794:209-215
pubmed: 27890711
Life Sci. 2018 Nov 15;213:18-24
pubmed: 30290188
J Vasc Res. 1999 Jul-Aug;36(4):311-20
pubmed: 10474044
Int J Mol Sci. 2020 Oct 17;21(20):
pubmed: 33080916
NeuroRx. 2005 Oct;2(4):541-53
pubmed: 16489364
J Cardiovasc Pharmacol. 2017 Jan;69(1):23-33
pubmed: 27676325
Sci Rep. 2017 Sep 21;7(1):12064
pubmed: 28935932
J Pharmacol Exp Ther. 2006 Nov;319(2):710-23
pubmed: 16857731
Naunyn Schmiedebergs Arch Pharmacol. 2020 May;393(5):813-827
pubmed: 31858155
Biomed Pharmacother. 2021 Mar;135:111164
pubmed: 33385856
Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14136-41
pubmed: 10570211
J Cell Physiol. 2019 Feb;234(2):1295-1299
pubmed: 30146778
Mol Pharmacol. 2003 Mar;63(3):699-705
pubmed: 12606780
Trends Pharmacol Sci. 2000 Jun;21(6):218-24
pubmed: 10838609
Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3353-63
pubmed: 23108552
Pharmacol Rev. 2006 Sep;58(3):389-462
pubmed: 16968947
Neurogastroenterol Motil. 2021 Mar;33(3):e14003
pubmed: 33058313
J Pharmacol Exp Ther. 2014 Apr;349(1):29-38
pubmed: 24431468
Biomolecules. 2020 Apr 29;10(5):
pubmed: 32365486
Antioxidants (Basel). 2019 Dec 25;9(1):
pubmed: 31881765
Pharmacol Biochem Behav. 2015 Jun;133:99-110
pubmed: 25847619
Int J Mol Sci. 2019 Nov 03;20(21):
pubmed: 31684173
Br J Pharmacol. 2010 Jun;160(3):594-603
pubmed: 20136843
Mol Nutr Food Res. 2016 Jan;60(1):92-102
pubmed: 26337420
Int J Mol Sci. 2018 Jul 08;19(7):
pubmed: 29986533
Fundam Clin Pharmacol. 2002 Apr;16(2):125-40
pubmed: 12031065
Biomed Pharmacother. 2018 Jul;103:157-166
pubmed: 29653360
J Psychopharmacol. 2011 Feb;25(2):274-80
pubmed: 19939866
ACS Med Chem Lett. 2020 Jun 17;11(10):2024-2031
pubmed: 33062188
Adv Exp Med Biol. 2021;1264:15-28
pubmed: 33332001
Bioorg Med Chem. 2007 Nov 15;15(22):6956-74
pubmed: 17827019
Adv Pharmacol. 2017;80:223-247
pubmed: 28826536
Br J Pharmacol. 2015 Feb;172(3):737-53
pubmed: 25257544
J Smooth Muscle Res. 2008 Apr;44(2):65-81
pubmed: 18552454
Pharmaceuticals (Basel). 2021 Mar 16;14(3):
pubmed: 33809564