106 M.E. Abood
agonists, that there is a complex molecular architecture of the cannabinoid recep-
tors. This arrangement allows for a single receptor to recognize multiple classes of
compounds and produce an array of distinct downstream effects. Natural polymor-
phisms and alternative splice variants may also contribute to the pharmacological
diversity of the cannabinoid receptors. As our knowledge of the distinct differ-
ences grows, we may be able to target select receptor conformations and their
corresponding pharmacological responses. Importantly, the basic biology of the
endocannabinoid system will continue to be revealed by ongoing investigations.
References
Abadji V, Lucas-Lenard J, Chin C, Kendall D (1999) Involvement of the carboxyl terminus of
the third intracellular loop of the cannabinoid CB1 receptor in constitutive activation
of Gs. J Neurochem 72:2032–2038
Abood ME, Sauss C, Fan F, Tilton CL, Martin BR (1993) Development of behavioral tolerance
to∆9-THC without alteration of cannabinoid receptor binding or mRNA levels in whole
brain. Pharmacol Biochem Behav 46:575–579
Abood ME, Ditto KA, Noel MA, Showalter VM, Tao Q (1997) Isolation and expression of
mouse CB1 cannabinoid receptor gene: comparison of binding properties with those
of native CB1 receptors in mouse brain and N18TG2 neuroblastoma cells. Biochem
Pharmacol 53:207–214
Alberich Jorda M, Rayman N, Tas M, Verbakel SE, Battista N, Van Lom K, Lowenberg B,
Maccarrone M, Delwel R (2004) The peripheral cannabinoid receptor Cb2, frequently
expressed on AML blasts, either induces a neutrophilic differentiation block or confers
abnormal migration properties in a ligand-dependent manner. Blood
Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P,
Ledbetter DH, Barker DF, Nakamura Y, et al (1989) Chromosome 17 deletions and p53
gene mutations in colorectal carcinomas. Science 244:217–221
Ballesteros JA, Weinstein H (1995) Integrated methods for the construction of three di-
mensional models and computational probing of structure function relations in G
protein-coupled receptors. In: Conn PM, Sealfon SM (eds) Methods in Neuroscience.
Academic Press, San Diego, pp 366–428
BasavarajappaBS,HungundBL(2001)Cannabinoidreceptoragonist-stimulated[35S]guano-
sine triphosphateγS binding in the brain of C57BL/6 and DBA/2 mice. J Neurosci Res
64:429–446
BenitoC,NunezE,TolonRM,CarrierEJ,RabanoA,HillardCJ,RomeroJ(2003)Cannabinoid
CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic
plaque-associated glia in Alzheimer’s disease brains. J Neurosci 23:11136–11141
Bonhaus D, Chang L, Kwan J, Martin G (1998) Dual activation and inhibition of adenylyl
cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of
intracellular responses. J Pharmacol Exp Ther 287:884–888
Bonner T (1996) Molecular biology of cannabinoid receptors. J Neuroimmunol 69:15–23
Bouaboula M, Bourrie B, Rinaldi-Carmona M, Shire D, Fur GL, Casellas P (1995) Stimulation
of Cannabinoid Receptor CB1 induces krox-24 expression in human astrocytoma cells.
J Biol Chem 270:13973–13980
Bouaboula M, Perrachon S, Milligan L, Canat X, Rinaldi-Carmona M, Portier M, Barth F,
Calandra B, Pecceu F, Lupker J, Maffrand J-P, LeFur G, Casellas P (1997) A selective
inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein
kinase activation stimulated by insulin or insulin-like growth factor 1. J Biol Chem
272:22330–22339