Biology Reference
In-Depth Information
Figure 1. Schematic summary of CB1 receptor signaling. CB1 receptors are 7-transmembrane domain,
G-protein-coupled proteins located in the cell membrane. The Ca2+ channels inhibited by CB1
receptors include N-, P/Q- and L-type channels. Actions on Ca2+ channels and adenylyl cyclase (AC)
are thought to be mediated by the α subunits of the G-protein, and those on GIRK and PI3K by the βγ
subunits. Inhibition of AC and the subsequent decrease in cAMP decreases activation of cAMP-
dependent protein kinase A (PKA), which leads to decreased phosphorylation of the K+ channels.
Stimulatory effects are shown by a (→) sign and inhibitory effects by a (⊥) sign
2.2 Endocannabinoids
The ECs are lipid signaling molecules that bind to and activate cannabinoid receptors.
These lipid compounds are formed from phospholipids precursors [17, 19, 20, 33, 61, 142]
within cells throughout the body, and are released from these cells on demand in a
nonvasicular manner to act in a paracrine fashion [17, 19, 20, 61, 76, 142].
Beginning in 1992, the first endogenous cannabinoid was identified as anandamide
(AEA, arachidonylethanolamide). It was named from the Sanskrit ananda, “internal bliss,''
making reference to its chemical structure (the amide of arachidonic acid and ethanolamine)
[57]. Subsequently, another endogenous cannabinoid receptor ligand, 2-arachidonylglycerol
(2-AG) was discovered and characterized [141, 187]. The third ether-type EC, 2-
arachidonylglycerol ether (noladin ether), was isolated from the CNS and shown to display
pharmacological properties similar to AEA [88]. The fourth type of EC, virodhamine, in
contrast to the previously described endocannabinoids, is a partial agonist with in vivo
antagonist activity at the CB1 receptor [168]. The fifth type of EC, N-arachidonyl-dopamine
(NADA), not only binds to CB1 receptor but also stimulates vanilloid receptors (VR1) [101].
It should be noted that except AEA and 2-AG, to date, there is little evidence about the
physiological actions of these compounds.
