Cannabinoid Receptors and Endocannabinoids: Evidence for New Players

Overview

Journal AAPS J

Specialty Pharmacology

Date 2006 Jun 27

PMID 16796380

Citations 109

Authors

Ken Mackie

Nephi Stella

Affiliations

Soon will be listed here.

Abstract

It is now well established that the psychoactive effects of Cannabis sativa are primarily mediated through neuronal CB1 receptors, while its therapeutic immune properties are primarily mediated through CB2 receptors. Two endocannabinoids, arachidonoylethanolamide and 2-arachidonoylglycerol, have been identified, their action on CB1 and CB2 thoroughly characterized, and their production and inactivation elucidated. However, many significant exceptions to these rules exist. Here we review the evidence suggesting that cannabinoids can modulate synaptic transmission, the cardiovascular system, and the immune system through receptors distinct from CB1 and CB2, and that an additional "independent" endocannabinoid signaling system that involves palmitoylethanolamide may exist.

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References

Breivogel C, Griffin G, Di Marzo V, Martin B . Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol. 2001; 60(1):155-63. View

Cravatt B, Demarest K, Patricelli M, Bracey M, Giang D, Martin B . Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci U S A. 2001; 98(16):9371-6. PMC: 55427. DOI: 10.1073/pnas.161191698. View

Stella N, Piomelli D . Receptor-dependent formation of endogenous cannabinoids in cortical neurons. Eur J Pharmacol. 2001; 425(3):189-96. DOI: 10.1016/s0014-2999(01)01182-7. View

Ueda N, Yamanaka K, Yamamoto S . Purification and characterization of an acid amidase selective for N-palmitoylethanolamine, a putative endogenous anti-inflammatory substance. J Biol Chem. 2001; 276(38):35552-7. DOI: 10.1074/jbc.M106261200. View

Hajos N, Ledent C, Freund T . Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience. 2001; 106(1):1-4. DOI: 10.1016/s0306-4522(01)00287-1. View

Conti S, Costa B, Colleoni M, Parolaro D, Giagnoni G . Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat. Br J Pharmacol. 2002; 135(1):181-7. PMC: 1573125. DOI: 10.1038/sj.bjp.0704466. View

Carlisle S, Marciano-Cabral F, Staab A, Ludwick C, Cabral G . Differential expression of the CB2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation. Int Immunopharmacol. 2002; 2(1):69-82. DOI: 10.1016/s1567-5769(01)00147-3. View

Alberich Jorda M, Verbakel S, Valk P, Maccarrone M, Lowenberg B, Delwel R . Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol. Blood. 2002; 99(8):2786-93. DOI: 10.1182/blood.v99.8.2786. View

Lambert D, Vandevoorde S, Jonsson K, Fowler C . The palmitoylethanolamide family: a new class of anti-inflammatory agents?. Curr Med Chem. 2002; 9(6):663-74. DOI: 10.2174/0929867023370707. View

10.

Walter L, Franklin A, Witting A, Moller T, Stella N . Astrocytes in culture produce anandamide and other acylethanolamides. J Biol Chem. 2002; 277(23):20869-76. DOI: 10.1074/jbc.M110813200. View

11.

McKallip R, Lombard C, Martin B, Nagarkatti M, Nagarkatti P . Delta(9)-tetrahydrocannabinol-induced apoptosis in the thymus and spleen as a mechanism of immunosuppression in vitro and in vivo. J Pharmacol Exp Ther. 2002; 302(2):451-65. DOI: 10.1124/jpet.102.033506. View

12.

Dinh T, Carpenter D, Leslie F, Freund T, Katona I, Sensi S . Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci U S A. 2002; 99(16):10819-24. PMC: 125056. DOI: 10.1073/pnas.152334899. View

13.

Giuffrida A, Parsons L, Kerr T, Rodriguez de Fonseca F, Navarro M, Piomelli D . Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci. 1999; 2(4):358-63. DOI: 10.1038/7268. View

14.

McCOY K, Matveyeva M, Carlisle S, Cabral G . Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation. J Pharmacol Exp Ther. 1999; 289(3):1620-5. View

15.

Walker J, Huang S, Strangman N, TSOU K . Pain modulation by release of the endogenous cannabinoid anandamide. Proc Natl Acad Sci U S A. 1999; 96(21):12198-203. PMC: 18435. DOI: 10.1073/pnas.96.21.12198. View

16.

Hashimotodani Y, Ohno-Shosaku T, Tsubokawa H, Ogata H, Emoto K, Maejima T . Phospholipase Cbeta serves as a coincidence detector through its Ca2+ dependency for triggering retrograde endocannabinoid signal. Neuron. 2005; 45(2):257-68. DOI: 10.1016/j.neuron.2005.01.004. View

17.

Gokoh M, Kishimoto S, Oka S, Mori M, Waku K, Ishima Y . 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces rapid actin polymerization in HL-60 cells differentiated into macrophage-like cells. Biochem J. 2004; 386(Pt 3):583-9. PMC: 1134878. DOI: 10.1042/BJ20041163. View

18.

Tsuboi K, Sun Y, Okamoto Y, Araki N, Tonai T, Ueda N . Molecular characterization of N-acylethanolamine-hydrolyzing acid amidase, a novel member of the choloylglycine hydrolase family with structural and functional similarity to acid ceramidase. J Biol Chem. 2005; 280(12):11082-92. DOI: 10.1074/jbc.M413473200. View

19.

Jordan J, He J, Eungdamrong N, Gomes I, Ali W, Nguyen T . Cannabinoid receptor-induced neurite outgrowth is mediated by Rap1 activation through G(alpha)o/i-triggered proteasomal degradation of Rap1GAPII. J Biol Chem. 2005; 280(12):11413-21. DOI: 10.1074/jbc.M411521200. View

20.

Begg M, Pacher P, Batkai S, Osei-Hyiaman D, Offertaler L, Mo F . Evidence for novel cannabinoid receptors. Pharmacol Ther. 2005; 106(2):133-45. DOI: 10.1016/j.pharmthera.2004.11.005. View