•  
  •  
 

Acta Universitatis Lodziensis, Folia Biologica et Oecologica

Abstract

The endocannabinoid system (ECS) consists of the endocannabinoids, cannabinoid receptors and the enzymes that synthesize and degrade endocannabinoids. The whole EC system plays an important role in the proper functioning of the central and autonomic nervous system. ECS is involved in the regulation of the body energy and in the functioning of the endocrine system. It can affect on the regulation of emotional states, motoric movement, operations of the endocrine, immune and digestive system. Many of the effects of cannabinoids are mediated by G coupled –protein receptors: CB1, CB2 and GPR55 but also of transient receptor potential channels (TRPs) which not only induce the sensation of pain but also support inflammation via secretion of pro-inflammatory neuropeptides. In this review work we briefly summarize the role and action of cannabinoid receptors CB1 and CB2, protein-coupled receptor 55 (GPR55) and transient receptor potential vanilloid 1 (TRPV1).

Polish Abstract

Układ endokannabinoidowy (ang. endocannabinoid stystem-ECS) składa się z receptorów kannabinoidowych CB1 i CB2, agonistów egzogennych i endogennych: kannabinoidów i endokannabinoidów oraz enzymów regulujące syntezę i degradację endogennych ligandów tego układu. Jest systemem biorącym udział w wielu procesach fizjologicznych organizmu. Odgrywa on istotną rolę w prawidłowym funkcjonowaniu centralnego i autonomicznego układu nerwowego. Układ endokannabinoidowy reguluje również m.in. gospodarkę energetyczną, aktywność motoryczną, układ endokrynny oraz układ hormonalny poprzez regulacje powiązań neurohormonalnych i neuroimmunologicznych. Wiele jego wspomnianych funkcji związanych jest z receptorami sprzężonymi z białkami G, takimi jak receptory CB1, CB2 czy GPR55. Co raz więcej mówi się również o znaczącej roli receptorów przejściowego potencjału TRPs (ang. transient receptor potential), które nie tylko pośredniczą w odczuwaniu bólu, ale także są odpowiedzialne za wspomaganie stanu zapalnego poprzez wydzielanie pro-zapalnych neuropeptydów. W niniejszej pracy przeglądowej postanowiliśmy krótko scharakteryzować oraz opisać rolę i działanie receptorów kannabinoidowych CB1 i CB2, receptora sprzężonego z białkiem G (GPR55) i receptora przejściowego potencjału waniloidowego (TRPV1).

Keywords

cannabinoid receptors, CB1, CB2, TRPV1, GPR55

References

Adam, J.M., Cairins, J., Caulfield, W., Cowley, P., Cumming, I., Easson, M., Edwards, D., Ferguson, M., Goodwin, R., Jeremiah, F. Kiyoi, T., Mistry, A., Moir, E., Morphy, R., Tierney, J., York, M., Baker, J., Cottney, J.E., Houghton, A.K., Westwood, P.J. & Walker, G. 2010. Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists. Medicinal Chemistry Communications, 1: 54–60.

Albert, P.R. 2011. What is a functional genetic polymorphism? Defining classes of functionality. The Journal of Psychiatry & Neuroscience, 36(6): 363–365.

Ameri, A. 1999. The effects of cannabinoids on the brain. Progress in Neurobiology, 58(4): 315–348.

Befort, K. 2015. Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies. Frontiers in Pharmacology, 5; 6: 6.

Bisogno, T., Hanus, L., De Petrocellis, L., Tchilibon, S., Ponde, D.E., Brandi, I., Moriello, A.S., Davis, J.B., Mechoulam, R. & Di Marzo V. 2001. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. British Journal of Pharmacology, 134(4): 845–852.

Brito, R., Sheth, S., Mukherjea, D., Rybak, L.P., Ramkumar, V. 2014. TRPV1: A Potential Drug Target for Treating Various Diseases. Cells, 3(2):517–545.

Busquets-Garcia, A., Soria-Gomez, E., Bellocchio, L., Marsicano, G. 2016. Cannabinoid receptor type-1: breaking the dogmas. F1000Reseearch, 5, F1000 Faculty Rev-990.

Cabral, G.A. & Griffin-Thomas, L. 2009. Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Reviews in Molecular Medicine, 20, 11:e3.

Cassano, T., Calcagnini S., Pace, L., De Marco, F., Romano, A., Gaetani, S. 2017. Cannabinoid Receptor 2 Signaling in Neurodegenerative Disorders: From Pathogenesis to a Promising Therapeutic Target. Frontiers in Neuroscience, 11: 30.

Clapham, D.E., Julius, D., Montell, C., Schultz, G. 2005. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacological Reviews, 57(4): 427–450.

Cui, M., Gosu, V., Basith, S., Hong, S., Choi, S. 2016. Polymodal Transient Receptor Potential Vanilloid Type 1 Nocisensor: Structure, Modulators, and Therapeutic Applications. Advances in Protein Chemistry and Structural Biology, 104: 81–125.

GeneBank, NCBI. Available from: https://www.ncbi.nlm.nih.gov/gene/7442

GeneBank, NCBI. Available from: https://www.ncbi.nlm.nih.gov/gene/9290

GeneCards. Available from: http://www.genecards.org/cgi-bin/carddisp.pl?gene=CNR2&keywords=cb1

GeneCards. Available from: http://www.genecards.org/cgi-bin/carddisp.pl?gene=CNR1&keywords=cb1

GeneCards. Available from: http://www.genecards.org/cgi-bin/carddisp.pl?gene=TRPV1

GeneCards. Available from: http://www.genecards.org/cgi-bin/carddisp.pl?gene=GPR55&keywords=GPR55

Gunthorpe, M.J., Szallasi, A. 2008. Peripheral TRPV1 Receptors As Targets for Drug Development: New Molecules and Mechanisms. Current Pharmaceutical Design, 14(1): 32–41.

Herrera, B., Carracedo, A., Diez-Zaera, M., Gomez del Pulgar, T., Guzman, M., Velasco, G. 2006. The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway. Experimental Cell Research, 312(11): 2121–2131.

Hille, B. 1978. Ionic channels in excitable membranes. Current problems and biophysical approaches. Biophysical Journal, (2): 283–294.

Howlett, A.C., Mukhopadhyay, S. 2000. Cellular signal transduction by anandamide and 2-arachidonoylglycerol. Chemistry and Physics of Lipids, 108(1–2): 53–70.

Ishiguro, H., Horiuchi Y., Ishikawa, M., Koga, M., Imai, K., Suzuki, Y., Morikawa, M., Inada, T. Watanabe, Y., Takahashi, M., Someya, T., Ujike, H., Iwata, N., Ozaki, N., Onaivi, E.S., Kunugi, H., Sasaki, T., Itokawa, M., Arai, M., Niizato, K., Iritani, S., Naka, I., Ohashi, J., Kakita, A., Takahashi, H., Nawa, H., Arinami, T. 2010. Brain cannabinoid CB2 receptor in schizophrenia. Biological Psychiatry, 67(10): 974–982.

Járai, Z, Wagner, J.A., Varga, K., Lake, K.D., Compton, D.R., Martin, B.R., Zimmer, A.M., Bonner, T.I., Buckley, N.E., Mezey, E., Razdan, R.K., Zimmer, A., Kunos, G. 1999. "Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proceedings of the National Academy of Sciences of the United States of America, 96 (24): 14136–41.

Johns, D.G., Behm, D.J., Walker, D.J., Ao, Z., Shapland, E.M., Daniels, D.A., Riddick, M., Dowel,l S., Staton, P.C., Green, P., Shabon, U., Bao, W., Aiyar, N., Yue, T.L., Brown, A.J., Morrison, A.D., Douglas, S.A. 2007. The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. British Journal of Pharmacology, 152 (5): 825–31.

Kazula, A. 2009. Zastosowanie naturalnych kannabinoidów i endokannabinoidów w terapii. Postępy farmakoterapii, 65(2): 147–160.

Komorowski, J., Stępień, H. 2007. Rola układu endokannabinoidowego w regulacji czynności dokrewnej i kontroli równowagi energetycznej człowieka. Postępy Higieny Medycyny Doświadczalnej, 61: 99–105.

Konarska, L., Ellert, A. 2004. Receptory kannabinoidowe. In: Nowak, J.Z., Zawilska, J.B. (eds). Receptory i mechanizmy przekazywania sygnału. Wydawnictwo Naukowe PWN, pp. 464–490.

Karjnik M., Żylicz Z. 2003. Kannabinoidy w medycynie paliatywnej. Polska Medycyna Paliatywna, 2: 123–131.

Laprairie, R.B., Kelly, M.E., Denovan-Wright, E.M. 2012. The dynamic nature of type 1 cannabinoid receptor (CB1) gene transcription. British Journal of Pharmacology, 167(8): 1583–1595.

Lauckner, J.E., Jensen, J.B., Chen, H.Y., Lu, H.C., Hille, B., Mackie, K. 2008. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proceedings of the National Academy of Sciences of the United States of America, 105: 2699–2704.

Lee, Y., Hong, S., Cui, M., Sharma, P.K., Lee, J., Choi, S. 2015. Transient receptor potential vanilloid type 1 antagonists: a patent review (2011-2014). Expert Opinion on Therapeutic Patents, 25(3): 291–318.

Liao, M., Cao, E., Julius, D., Cheng Y. 2013. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature, 504: 107–112.

Lishko, P.V., Procko, E., Jin, X., Phelps, C.B., Gaudet R. 2007. The Ankyrin Repeats of TRPV1 Bind Multiple Ligands and Modulate Channel Sensitivity. Neuron, 54: 905–918.

Mackie, K., Stella, N. 2006. Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS Journal, 8(2): E298–306.

Martínez, N., Abán, C.E., Leguizamón, G.F., Damiano, A.E., Farina, M.G. 2016. TPRV-1 expression in human preeclamptic placenta. Placenta, 40: 25–28.

McHugh, D., Tanner, C., Mechoulam, R., Pertwee, R.G., Ross, R.A., 2008. Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2. Molecular Pharmacology, 73 (2): 441–50.

McKallip, R.J., Lombard, C., Fisher, M., Martin, B.R., Ryu, S., Grant, S., Nagarkatti, P.S., Nagarkatti M. 2002. Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood, 100(2): 627–634.

Navarrete, F.., Rodríguez-Arias, M., Martín-García, E., Navarro, D., García-Gutiérrez, M.S., Aguilar, M.A., Aracil-Fernández, A., Berbel, P., Miñarro, J., Maldonado, R., Manzanares, J. 2013. Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotine. Neuropsychopharmacology, 38(12): 2515–2524.

Nicoll, G., Davidson, S., Shanley, L., Hing, B., Lear, M., McGuffin, P., Ross, R., MacKenzie, A. 2012. Allele-specific differences in activity of a novel cannabinoid receptor 1 (CNR1) gene intronic enhancer in hypothalamus, dorsal root ganglia, and hippocampus. The Journal of Biological Chemistry, 287(16): 12828–12834.

Nilius, B., Owsianik, G. 2011. The transient receptor potential family of ion channels. Genome Biology, 12(3): 218.0.

Numazaki, M., Tominaga, T., Takeuchi, K., Murayama, N., Toyooka, H., Tominaga, M. 2003. Structural determinant of TRPV1 desensitization interacts with calmodulin. Proceedings of the National Academy of Sciences of the United States of America, 100(13):8002–8006.

Pawlak, M., Łaczmański, Ł., Milewicz, A. 2011. Rola układu endokannabinoidowego i polimorfizmów genu CNR1 w powstawaniu otyłości. Endokrynologia, Otyłość i Zaburzenia Przemiany Materii, 7(3): 192–196.

Pertwee, R.G. 2006. Cannabinoid pharmacology: the first 66 years. British Journal of Pharmacology, 147: 163–171.

Pertwee, R.G. 2009. Emerging strategies for exploiting cannabinoid receptor agonists as medicines. British Journal of Pharmacology, 156(3): 397–411.

Pietrzak, B., Dunaj, A., Piątkowska, K. 2011. Rola układu kannabinoidowego w patogenezie oraz poszukiwaniu nowych możliwości farmakoterapii zespołu zależności alkoholowej. Postępy Higieny Medycyny Doświadczalnej, 65: 606–615.

Racz, I., Nadal, X., Alferink, J., Baños, J.E., Rehnelt, J., Martín, M., Pintado, B., Gutierrez-Adan, A., Sanguino, E., Manzanares, J., Zimmer, A., Maldonado, R. 2008. Crucial Role of CB2 cannabinoid receptor in the regulation of central immune responses during neuropathic pain. Journal of Neuroscience, 28(46): 12125–12135.

Rutkowska, M., Jamontt, J. 2005. Rola układu kannabinoidowego w fizjologii i patofizjologii ośrodkowego układu nerwowego. Advances in Clinical and Experimental Medicine, 14(6): 1243–1252.

Ryberg, E., Vu, H.K., Larsson, N., Groblewski, T., Hjorth, S., Elebring, T., Sjögren, S., Greasley, P.J. 2005. Identification and characterisation of novel splice variant of the human CB1 receptor. FEBS Letters, 579(1): 259–264.

Ryberg, E., Larsson, N., Sjögren, S., Hjorth, S., Hermansson, N.O., Leonova, J., Elebring, T., Nilsson, K., Drmota, T. & Greasley, P.J. 2007. The orphan receptor GPR55 is a novel cannabinoid receptor. British Journal of Pharmacology, 152(7): 1092–1101.

Sawzdargo, M., Nguyen, T., Lee, D.K., Lynch, K.R., Cheng, R., Heng, H.H., George, S.R., O’Dowd, B.F. 1999. Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain research. Molecular brain research, 64(2): 193–198.

Shire, D., Carillon, C., Kaghad, M., Calandra, B., Rinaldi-Carmona, M., Le Fur, G., Caput, D., Ferrara, P. 1995. An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. The Journal of Biological Chemistry, 270(3): 3726–3731.

Shore, D.M., Reggio, P.H. 2015. The therapeutic potential of orphan GPCRs, GPR35 and GPR55. Frontiers in Pharmacology, 6: 69.

Simcocks, A.C., O’keefe, L., Jenkin, K.A., Mathai, M.L., Hryciw, D.H., Mcainch, A.J. 2014. A potential role for GPR55 in the regulation of energy homeostasis. Drug Discovery Today, 19:1145–1151.

Staruschenko, A., Jeske, N.A., Akopian, A.N. 2010. Contribution of TRPV1-TRPA1 Interaction to the Single Channel Properties of the TRPA1 Channel. The Journal of Biological Chemistry, 285: 15167–15177.

Sullivan, J.M. 2000. Cellular and molecular mechanisms underlying learning and memory imrairments produced by cannabinoids. Learning & Memory, 7(3): 132–139.

Szallasi, A., Cortright, D.N., Blum, C.A., Eid, S.R. 2007, The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nature Reviews Drug Discovery, 6: 357–372.

Tilley, D.G. 2011. G protein-dependent and G protein-independent signaling pathways and their impact on cardiac function. Circulation Research, 109(2): 217–230.

U.S. National Institutes of Health, 2013. https://clinicaltrials.gov

Zhang, H.Y., Gao, M., Liu, Q.R., Bi, G.H., Li, X., Yang, H.J., Gardner, E.L., Wu, J., Xi, Z.X. 2014. Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Proceedings of the National Academy of Sciences of the United States of America, 111(46): E5007–15.

Zoratti, C., Kipmen-Korgun, D., Osibow, K., Malli, R., Graier, W.F. 2003. Anandamide initiates Ca(2+) signaling via CB2 receptor linked to phospholipase C in calf pulmonary endothelial cells. British Journal of Pharmacology, 140(8): 1351–1362.

Zygmunt, P.M., Petersson, J., Andersson, D.A., Chuang, H.H., Sørgård, M., Di Marzo, V., Julius, D., Högestätt, E.D. 1999. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature, 400: 452–457.

First Page

1

Last Page

13

Language

eng

Included in

Biology Commons

Share

COinS