An antagonist binds that to a GPR55 receptor and stops or slows the expected response an agonist at the same site would induce (see below).
For example, THC is an agonist at GPR55 while CBD is an antagonist at the same receptor thus producing opposing results even though they bind the same type of receptor.
General GPR55 Antagonism Associated Effects
CID16020046 blocks the effect of lysophosphatidylinositol (LPI) at its receptor, GPR55 (B. Okine et al., 2018).1
GPR55 Antagonism and Cancer
May protect against some forms of cancer.
GPR55/LPI axis is considered a novel target for cancer therapeutics (R. Ross, 2011).2
Antagonism at GPR55 may induce antitumor effects via the reduction of the MEK/ERK and PI3K-AKT pathways (N. Singh et al., 2016).3
CID16020046 produces antitumor effects (N. Singh et al., 2017).4
(R,R’)-4’-methoxy-1-naphthylfenoterol (MNF) produces antitumor effects (N. Singh et al., 2017).4
GPR55 Antagonism and Neurological Diseases
Data suggest that the use of GPR55 antagonists may serve in the treatment of neuroinflammation-, and neurodegeneration-related diseases (S. Saliba et al., 2018).5
GPR55 Antagonism and Gastrointestinal Diseases
GPR55 antagonists may protect against intestinal inflammation (colitis) (A. Stančić et al., 2015).6
GPR55 Antagonists
Cannabidiol (CBD) EC50 445±67nM (E. Ryberg et al., 2007)7
CID16020046 (A. Brown et al., 2018).8
(R,R’)-4’-methoxy-1-naphthylfenoterol (MNF) (R. Paul et al., 2013).9
KIT 17 (S. Saliba et al., 2018).10
Endnotes:
1. Brown AJ, Castellano-Pellicena I, Haslam CP, Nichols PL, Dowell SJ. Structure-Activity Relationship of the GPR55 Antagonist, CID16020046. Pharmacology. 2018;102(5-6):324-331.
2. Ross RA. (2011) L-α-lysophosphatidylinositol meets GPR55: a deadly relationship. Trends Pharmacol Sci. 32(5):265-9.
3. Singh NS, Bernier M, Wainer IW. Selective GPR55 antagonism reduces chemoresistance in cancer cells. Pharmacol Res. 2016 Sep;111:757-766.
4. Singh NS, Bernier M, Wainer IW. Selective GPR55 antagonism reduces chemoresistance in cancer cells. Pharmacol Res. 2016 Sep;111:757-766.
5. Saliba, S.W., Jauch, H., Gargouri, B. et al. Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells. J Neuroinflammation 15, 322 (2018).
6. Stančić, A., Jandl, K., Hasenöhrl, C., Reichmann, F., Marsche, G., Schuligoi, R., Heinemann, A., Storr, M. and Schicho, R. (2015), The GPR55 antagonist CID16020046 protects against intestinal inflammation. Neurogastroenterol. Motil., 27: 1432-1445
7. Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007 Dec;152(7):1092-101.
8. Brown AJ, Castellano-Pellicena I, Haslam CP, Nichols PL, Dowell SJ. Structure-Activity Relationship of the GPR55 Antagonist, CID16020046. Pharmacology. 2018;102(5-6):324-331.
9. Paul RK, Wnorowski A, Gonzalez-Mariscal I, Nayak SK, Pajak K, Moaddel R, Indig FE, Bernier M, Wainer IW. (R,R’)-4′-methoxy-1-naphthylfenoterol targets GPR55-mediated ligand internalization and impairs cancer cell motility. Biochem Pharmacol. 2014 Feb 15;87(4):547-61.
10. Saliba, S.W., Jauch, H., Gargouri, B. et al. Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells. J Neuroinflammation 15, 322 (2018).
