Cannabinoid Receptors and Their Ligands in Brain and Other Tissues

  • Roger G. Pertwee


Mammalian tissues contain two types of cannabinoid receptor, CB1 and CB2, both coupled to their effector systems through Gi1i/0 proteins. CB1 receptors are present in the central nervous system as well as in certain neuronal and nonneuronal peripheral tissues. Some CB1 receptors occur at nerve terminals where they modulate transmitter release when activated. CB2 receptors are found mainly in cells of the immune system. The possibility that mammalian tissues express additional cannabinoid receptor types of physiological significance cannot be excluded. Indeed, preliminary pharmacological evidence supporting this possibility already exists. Endogenous ligands for cannabinoid receptors have also been discovered, the most important being arachidonoylethanolamide and 2-arachidonoyl glycerol. These ligands and their receptors constitute the endogenous cannabinoid system. The discovery of this system has important physiological, pathophysiological, pharmacological, and therapeutic implications. Already selective CB1- and CB2-receptor agonists and antagonists have been developed and two cannabinoid receptor agonists, ∆9-tetrahydrocannabinol and nabilone, are used clinically as antiemetics or to boost appetite. Additional therapeutic uses of cannabinoid receptor agonists may include the suppression of some multiple sclerosis and spinal injury symptoms and the management of glaucoma, bronchial asthma, pain, and inflammatory disorders. One possible therapeutic strategy for the future is the development and use of drugs that activate cannabinoid receptors indirectly by modulating extracellular levels of endogenous cannabinoids. CB1-receptor agonists that do not cross the blood-brain barrier or whose potency is determined more by affinity than efficacy may also have clinical potential.


Fatty Acid Amide Hydrolase General Fatty Acid Amide Hydrolase Modulate Transmitter Release Noid Receptor Methyl Arachidonyl Fluorophosphonate 
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© Springer Science+Business Media New York 1999

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  • Roger G. Pertwee

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