Checkpoint 2: Endogenous Ligands

1Which of the following statements accurately characterizes the intrinsic efficacy and receptor profile of the endocannabinoid 2-arachidonoylglycerol (2-AG) compared to N-arachidonoylethanolamine (anandamide, AEA)?

A. 2-AG acts as a full agonist at both CB1 and CB2 receptors, whereas AEA acts as a partial agonist at these receptors. ✓ B. AEA acts as a full agonist at both CB1 and CB2 receptors, whereas 2-AG acts as a competitive antagonist at CB2 receptors. C. Both AEA and 2-AG are high-efficacy full agonists at CB1 receptors, but 2-AG lacks binding affinity for CB2 receptors. D. AEA is maintained at significantly higher physiological concentrations than 2-AG in the central nervous system.

Explanation: 2-Arachidonoylglycerol (2-AG) is present in higher physiological concentrations in the central nervous system than AEA and functions as a full agonist at both CB1 and CB2 receptors. In contrast, N-arachidonoylethanolamine (anandamide/AEA) displays high affinity for CB1 receptors but functions as a partial agonist with lower intrinsic efficacy at both CB1 and CB2 receptors.

2Regarding the enzymatic inactivation pathways of endocannabinoids, which of the following statements correctly describe the roles of FAAH and MAGL? (Select all that apply)

Select all that apply

A. Fatty acid amide hydrolase (FAAH) is the primary enzyme responsible for the hydrolytic cleavage of AEA into arachidonic acid and ethanolamine. ✓ B. Monoacylglycerol lipase (MAGL) is predominantly localized presynaptically and hydrolyzes 2-AG into arachidonic acid and glycerol. ✓ C. Pharmacological inhibition of FAAH causes selective accumulation of 2-AG without altering tissue levels of AEA. D. Targeted inhibition of MAGL elevates central concentrations of 2-AG, enhancing retrograde CB1 receptor signaling. ✓

Explanation: FAAH primarily metabolizes AEA into arachidonic acid and ethanolamine. MAGL is localized presynaptically and metabolizes 2-AG into arachidonic acid and glycerol. Inhibiting MAGL selectively increases central 2-AG levels, which prolongs retrograde activation of presynaptic CB1 receptors. Statement C is incorrect because FAAH inhibition selectively elevates AEA (and related N-acylethanolamines), whereas MAGL inhibition selectively elevates 2-AG.

Clinical Disclaimer

This course is for veterinary continuing education. It does not constitute veterinary advice or a recommendation to prescribe any specific product. No therapeutic claims are made for unapproved products.