To date, the only two monoacylglycerol derivatives that have been identified as endogenous ligands for cannabinoid receptors in the CNS are 2-arachidonyl glycerol (2-AG) and 2-arachidonyl glyceryl ether (nolandin ether; 2-AGE; Fezza et al., 2002; Hanus et al., 2001). 2-AG is synthesized from phosphatidyl inositol (PI) precursors via a PI-specific phosoholipase C (PLC) and diacylglycerol lipase (DAGL; Stella et al., 1997), but the synthetic pathway for 2-AGE has yet to be determined. In addition to the lipid-derived transmitters of the EC system, other putative and novel ligands of cannabinoid receptors have been discovered. Hemopressin, a peptide derived from cleavage of α-hemoglobin, acts an inverse agonist at the CB1 receptor (Heimann et al., 2007), and recently discovered N-terminally extended hemopressin-like peptides derived from both α- and β-hemoglobin have been found to act as CB1 agonists (Gomes et al., 2009). Interestingly, these peptide agonists produce activation of distinct signal transduction cascades from those of the lipid-derived transmitters suggesting that the functional consequences of CB1 activation are determined by the ligand. However, the relevance of these peptides for physiological processes is unclear, at
