The Therapeutic Potential of Novel Cannabinoid Receptors

Overview

Journal Pharmacol Ther

Specialty Pharmacology

Date 2009 Mar 3

PMID 19248809

Citations 33

Authors

Faith R Kreitzer

Nephi Stella

Affiliations

Soon will be listed here.

Abstract

Cannabinoids produce a plethora of biological effects, including the modulation of neuronal activity through the activation of CB(1) receptors and of immune responses through the activation of CB(2) receptors. The selective targeting of either of these two receptor subtypes has clear therapeutic value. Recent evidence indicates that some of the cannabinomimetic effects previously thought to be produced through CB(1) and/or CB(2) receptors, be they on neuronal activity, on the vasculature tone or immune responses, still persist despite the pharmacological blockade or genetic ablation of CB(1) and/or CB(2) receptors. This suggests that additional cannabinoid and cannabinoid-like receptors exist. Here we will review this evidence in the context of their therapeutic value and discuss their true belonging to the endocannabinoid signaling system.

Citing Articles

Divergent input patterns to the central lateral amygdala play a duet in fear memory formation.

Gao J, Liu Y, Xu H, Wu K, Zhang L, Cheng P iScience. 2024; 27(10):110886.

PMID: 39319272 PMC: 11421289. DOI: 10.1016/j.isci.2024.110886.

Endocannabinoid System Receptors at the Hip and Stifle Joints of Middle-Aged Dogs: A Novel Target for the Therapeutic Use of Extract in Canine Arthropathies.

Zamith Cunha R, Salamanca G, Mille F, Delprete C, Franciosi C, Piva G Animals (Basel). 2023; 13(18).

PMID: 37760233 PMC: 10525782. DOI: 10.3390/ani13182833.

Expression of cannabinoid (CB1 and CB2) and cannabinoid-related receptors (TRPV1, GPR55, and PPARα) in the synovial membrane of the horse metacarpophalangeal joint.

Zamith Cunha R, Zannoni A, Salamanca G, Silva M, Rinnovati R, Gramenzi A Front Vet Sci. 2023; 10:1045030.

PMID: 36937015 PMC: 10020506. DOI: 10.3389/fvets.2023.1045030.

Design, synthesis, and evaluation of substituted alkylindoles that activate G protein-coupled receptors distinct from the cannabinoid CB and CB receptors.

Kline T, Xu C, Kreitzer F, Hurst D, Eldeeb K, Wager-Miller J Eur J Med Chem. 2023; 249:115123.

PMID: 36708677 PMC: 10917149. DOI: 10.1016/j.ejmech.2023.115123.

Cannabinoid receptors in the inflammatory cells of canine atopic dermatitis.

Chiocchetti R, Salamanca G, Silva M, Gobbo F, Aspidi F, Zamith Cunha R Front Vet Sci. 2022; 9:987132.

PMID: 36187821 PMC: 9521433. DOI: 10.3389/fvets.2022.987132.

References

Ruiu S, Pinna G, Marchese G, Mussinu J, Saba P, Tambaro S . Synthesis and characterization of NESS 0327: a novel putative antagonist of the CB1 cannabinoid receptor. J Pharmacol Exp Ther. 2003; 306(1):363-70. DOI: 10.1124/jpet.103.049924. View

Hillard C, Manna S, Greenberg M, DiCamelli R, Ross R, Stevenson L . Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1). J Pharmacol Exp Ther. 1999; 289(3):1427-33. View

Mechoulam R, GAONI Y . The absolute configuration of delta-1-tetrahydrocannabinol, the major active constituent of hashish. Tetrahedron Lett. 1967; 12:1109-11. DOI: 10.1016/s0040-4039(00)90646-4. View

Ross R, Coutts A, McFarlane S, Anavi-Goffer S, Irving A, Pertwee R . Actions of cannabinoid receptor ligands on rat cultured sensory neurones: implications for antinociception. Neuropharmacology. 2000; 40(2):221-32. DOI: 10.1016/s0028-3908(00)00135-0. View

Price M, Baillie G, Thomas A, Stevenson L, Easson M, Goodwin R . Allosteric modulation of the cannabinoid CB1 receptor. Mol Pharmacol. 2005; 68(5):1484-95. DOI: 10.1124/mol.105.016162. View

Zondag G, Postma F, Etten I, Verlaan I, Moolenaar W . Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. Biochem J. 1998; 330 ( Pt 2):605-9. PMC: 1219179. DOI: 10.1042/bj3300605. View

Kohama T, Olivera A, Edsall L, Nagiec M, Dickson R, Spiegel S . Molecular cloning and functional characterization of murine sphingosine kinase. J Biol Chem. 1998; 273(37):23722-8. DOI: 10.1074/jbc.273.37.23722. View

Wise A, Gearing K, Rees S . Target validation of G-protein coupled receptors. Drug Discov Today. 2002; 7(4):235-46. DOI: 10.1016/s1359-6446(01)02131-6. View

Sawzdargo M, Nguyen T, Lee D, Lynch K, Cheng R, Heng H . Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain Res Mol Brain Res. 1999; 64(2):193-8. DOI: 10.1016/s0169-328x(98)00277-0. View

10.

Oz M . Receptor-independent effects of endocannabinoids on ion channels. Curr Pharm Des. 2006; 12(2):227-39. DOI: 10.2174/138161206775193073. View

11.

Heiber M, Docherty J, Shah G, Nguyen T, Cheng R, Heng H . Isolation of three novel human genes encoding G protein-coupled receptors. DNA Cell Biol. 1995; 14(1):25-35. DOI: 10.1089/dna.1995.14.25. View

12.

Rockwell C, Snider N, Thompson J, Vanden Heuvel J, Kaminski N . Interleukin-2 suppression by 2-arachidonyl glycerol is mediated through peroxisome proliferator-activated receptor gamma independently of cannabinoid receptors 1 and 2. Mol Pharmacol. 2006; 70(1):101-11. DOI: 10.1124/mol.105.019117. View

13.

Lastres-Becker I, Fezza F, Cebeira M, Bisogno T, Ramos J, Milone A . Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington's disease. Neuroreport. 2001; 12(10):2125-9. DOI: 10.1097/00001756-200107200-00017. View

14.

Zygmunt P, Petersson J, Andersson D, Chuang H, Sorgard M, Di Marzo V . Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 1999; 400(6743):452-7. DOI: 10.1038/22761. View

15.

Zhang H, Desai N, Olivera A, Seki T, Brooker G, Spiegel S . Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol. 1991; 114(1):155-67. PMC: 2289065. DOI: 10.1083/jcb.114.1.155. View

16.

Mo F, Offertaler L, Kunos G . Atypical cannabinoid stimulates endothelial cell migration via a Gi/Go-coupled receptor distinct from CB1, CB2 or EDG-1. Eur J Pharmacol. 2004; 489(1-2):21-7. DOI: 10.1016/j.ejphar.2004.02.034. View

17.

Park K, Kim M, Lee H, Kim S, Lee S, Kim J . S1P stimulates chemotactic migration and invasion in OVCAR3 ovarian cancer cells. Biochem Biophys Res Commun. 2007; 356(1):239-44. DOI: 10.1016/j.bbrc.2007.02.112. View

18.

Katona I, Freund T . Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med. 2008; 14(9):923-30. DOI: 10.1038/nm.f.1869. View

19.

Liu H, Sugiura M, Nava V, Edsall L, Kono K, Poulton S . Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J Biol Chem. 2000; 275(26):19513-20. DOI: 10.1074/jbc.M002759200. View

20.

Olivera A, Kohama T, Edsall L, Nava V, Cuvillier O, Poulton S . Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival. J Cell Biol. 1999; 147(3):545-58. PMC: 2151183. DOI: 10.1083/jcb.147.3.545. View