Two Brain-Derived Ethanolamides Inhibited Isolated Mouse Tissue and Shared THC Cross-Tolerance
Two endogenous fatty-acid ethanolamides inhibited electrically evoked contractions in isolated mouse vas deferens. Tissue obtained after THC pretreatment was less responsive. The experiment added functional evidence beyond receptor binding alone.
Binding and a functional response are different observations
The study examined ethanolamides designated anandamide 20:3 and 22:4, which had previously been identified in porcine brain and shown to bind cannabinoid sites. In isolated mouse tissue, both reduced an electrically evoked twitch response. Demonstrating a response in tissue strengthens an agonist hypothesis, although it does not establish every physiological role of the molecules.
THC pretreatment changed later tissue sensitivity
Vasa deferentia from THC-pretreated mice showed tolerance to the inhibitory effects of both compounds. The pretreatment was known to induce cannabinoid tolerance. This cross-tolerance supports a functional relationship, but does not by itself prove that the compounds have identical receptor affinity, metabolism or whole-animal effects.
The preparation limits the clinical inference
The measured endpoint was contraction of isolated reproductive-tract tissue, not fertility, sexual behavior or subjective intoxication. Identifying compounds in pig brain and testing their actions in mouse tissue also involves different biological contexts. Neither observation quantifies their normal contribution to human signaling.
Interpreting the evidence
This study helps distinguish chemical presence, receptor binding and functional activity. Its isolated-tissue findings should not be converted into a human reproductive diagnosis or a prediction of cannabis impairment.
Related reading: endogenous ligands administered as experimental drugs.
Research reference
Pertwee R; Griffin G; Hanus L; et al. (1994). Effects of two endogenous fatty acid ethanolamides on mouse vasa deferentia. European journal of pharmacology. doi:10.1016/0014-2999(94)90499-5. Evidence basis: study abstract.
