The authors contributed equally.
Endogenous cannabinoid anandamide inhibits nicotinic acetylcholine receptor function in mouse thalamic synaptosomes
Article first published online: 11 JAN 2008
© 2008 International Society for Neurochemistry. No claim to original US government works
Journal of Neurochemistry
Volume 105, Issue 4, pages 1235–1243, May 2008
How to Cite
Butt, C., Alptekin, A., Shippenberg, T. and Oz, M. (2008), Endogenous cannabinoid anandamide inhibits nicotinic acetylcholine receptor function in mouse thalamic synaptosomes. Journal of Neurochemistry, 105: 1235–1243. doi: 10.1111/j.1471-4159.2008.05225.x
- Issue published online: 11 JAN 2008
- Article first published online: 11 JAN 2008
- Received September 17, 2007; revised manuscript received December 7, 2007; accepted January 1, 2008.
- nicotinic receptor;
- thalamic synaptosomes
The effects of the endogenous cannabinoid anandamide [arachidonylethanolamide (AEA)] on the function of nicotinic acetylcholine receptor (nAChR) were investigated using the 86Rb+ efflux assay in thalamic synaptosomes. AEA reversibly inhibited 86Rb+ efflux induced by 300 μM ACh with an IC50 value of 0.9 ± 2 μM. Pre-treatment with the cannabinoid (CB1) receptor antagonist SR141716A (1 μM), the CB2 receptor antagonist SR144528 (1 μM), or pertussis toxin (0.2 mg/mL) did not alter the inhibitory effects of AEA, suggesting that known CB receptors are not involved in AEA inhibition of nAChRs. AEA inhibition of 86Rb+ efflux was not reversed by increasing acetylcholine (ACh) concentrations. In radioligand binding studies, the specific binding of [3H]-nicotine was not altered in the presence of AEA, indicating that AEA inhibits the function of nAChR in a non-competitive manner. Neither the amidohydrolase inhibitor phenylmethylsulfonyl fluoride (0.2 mM) nor the cyclooxygenase inhibitor, indomethacin, (5 μM) affected AEA inhibition of nAChRs, suggesting that the effect of AEA is not mediated by its metabolic products. Importantly, the extent of AEA inhibition of 86Rb+ efflux was significantly attenuated by the absence of 1% fatty acid free bovine serum albumin pre-treatment, supporting previous findings that fatty acid-like compounds modulate the activity of nAChRs. Collectively, the results indicate that AEA inhibits the function of nAChRs in thalamic synaptosomes via a CB-independent mechanism and that the background activity of these receptors is affected by fatty acids and AEA.