ABSTRACT
Cannabinoid ligands are implicated in many physiological processes and to date two receptors have been identified. However, a growing body of evidence exists that suggests the presence of additional receptors. Whilst cloning the previously described hCB1a, we have identified a novel variant that we call hCB1b. Characterising these two splice variants demonstrates that they have a unique pharmacological profile and that their RNA's are expressed at low levels in a variety of tissues.
Subject(s)
Alternative Splicing , Receptor, Cannabinoid, CB1/genetics , Amino Acid Sequence , Binding, Competitive , Cannabinoids/chemistry , Cannabinoids/pharmacology , Cell Membrane/chemistry , Cell Membrane/drug effects , Gene Expression , Gene Library , Guanosine 5'-O-(3-Thiotriphosphate)/chemistry , Humans , Ligands , Molecular Sequence Data , Receptor, Cannabinoid, CB1/metabolismABSTRACT
Cannabinoids have been considered for some time as potent therapeutic agents in chronic pain management. Central and systemic administration of natural, synthetic and endogenous cannabinoids produce antinociceptive and antihyperalgesic effects in both acute and chronic animal pain models. Although much of the existing data suggest that the analgesic effects of cannabinoids are mediated via neuronal CB1 receptors, there is increasing evidence to support a role for peripheral CB2 receptors, which are expressed preferentially on immune cells. As yet, little is known about the central contribution of CB2 in neuropathic pain states. We report here that chronic pain models associated with peripheral nerve injury, but not peripheral inflammation, induce CB2 receptor expression in a highly restricted and specific manner within the lumbar spinal cord. Moreover, the appearance of CB2 expression coincides with the appearance of activated microglia.
