Molecular Biology of Cannabinoid Receptors 85Fig. 1.A helix net representation of the human CB 1 receptor. The amino acids shared with the CB 2 receptor
areshaded
a two-digit decimal. The most highly conserved residue in each helix is assigned a
value of 0.50 and the other residues numbered relative to the conserved residue.
Transfected cell lines expressing the CB 2 receptor have an affinity for CP 55,940
that is similar to those expressing the CB 1 receptor (Felder et al. 1995; Munro et
al. 1993; Showalter et al. 1996). Furthermore, the affinities for∆^9 -THC, 11-OH-∆^9 -
THC, anandamide and cannabidiol at the CB 2 receptor are comparable to the brain
(Showalter et al. 1996) receptor. In contrast, cannabinol (which is known to be ten
times less potent than∆^9 -THCattheCB 1 receptor) was found to be equipotent to
∆^9 -THCattheCB 2 receptor (Showalter et al. 1996). Based on these binding profiles,
it was concluded that the peripheral receptor clone may be a cannabinoid receptor
subtype. Indeed, a more extensive characterization of this receptor demonstrates
a separation of pharmacological selectivities (Felder et al. 1995; Showalter et al.
1996; Slipetz et al. 1995). The compounds that have been identified as CB 1 and CB 2
selective serve as lead compounds in the design of even more selective ligands.
The affinity of SR141716A (the CB 1 receptor antagonist) is at least 50-fold higher
at the CB 1 receptor than at the CB 2 receptor (Felder et al. 1995; Rinaldi-Carmona
et al. 1994; Showalter et al. 1996) and has provided a starting point for the design
of more selective antagonists and agonists.