Allosteric modulation of G-protein–coupled receptors represents a key goal of current
pharmacology. In particular, endogenous allosteric modulators might represent important
targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of
drugs. Here we show that the anti-inflammatory lipid lipoxin A4 is an endogenous allosteric
enhancer of the CB1 cannabinoid receptor. Lipoxin A4 was detected in brain tissues, did not
compete for the orthosteric binding site of the CB1 receptor (vs. 3H-SR141716A), and did …

… Here we show that the anti-inflammatory lipid lipoxin A4 is an endogenous allosteric
enhancer of the CB1 cannabinoid receptor. Lipoxin A4 was detected in brain tissues, did not
compete for the orthosteric binding site of the CB1 receptor (vs. 3H-SR141716A), and did not
alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced
affinity of anandamide at the … Altogether, our results strongly suggest that LXA4 is an
endogenous allosteric modulator of the CB1 receptor that specifically enhances AEA signaling. …