Anandamides inhibit binding to the muscarinic acetylcholine receptor

@article{Lagalwar2007AnandamidesIB,
  title={Anandamides inhibit binding to the muscarinic acetylcholine receptor},
  author={Sarita Lagalwar and Elizabeth Z. Bordayo and Karen L. Hoffmann and John R. Fawcett and William H. Frey},
  journal={Journal of Molecular Neuroscience},
  year={2007},
  volume={13},
  pages={55-61}
}
Loss of memory and cholinergic transmission are associated with both Alzheimer’s disease (AD) and marijuana use. The human brain muscarinic acetylcholine receptor (mAChR), which is involved in memory function and is inhibited by arachidonic acid, is also inhibited by anandamides. Two agonists of the cannabinoid receptor derived from arachidonic acid, anandamide (AEA) and R-methanandamide, inhibit ligand binding to the mAChR. Binding of the mAChR antagonist [3H]quinuclidinyl benzilate ([3H]QNB… 
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1
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References

SHOWING 1-10 OF 30 REFERENCES
Inhibition of antagonist and agonist binding to the human brain muscarinic receptor by arachidonic acid
TLDR
The feedback inhibition of the mAChR by AA may serve a homeostatic function similar to the reuptake and hydrolysis of acetylcholine following cholinergic nerve transmission.
Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor.
TLDR
The present study revealed that the pharmacological activity of anandamide might be partially mediated through the 5-HT receptor.
Characterization of nicotine binding in mouse brain and comparison with the binding of alpha-bungarotoxin and quinuclidinyl benzilate.
TLDR
Differences in site densities, regional distribution, inhibitor potencies, and thermal denaturation indicated that nicotine binding was not the same as either QNB or alpha-BTX binding, and therefore that receptors for nicotine may represent a unique population of cholinergic receptors.
(R)-methanandamide: a chiral novel anandamide possessing higher potency and metabolic stability.
TLDR
Determination of the cannabinoid binding affinity in the presence and absence of the protease inhibitor phenylmethanesulfonyl fluoride (PMSF) revealed that (R)-methanandamide possesses a remarkable stability to aminopeptidase hydrolysis, and experiments with mice have demonstrated that it possesses cannabimimetric properties in vivo.
Functional role of high-affinity anandamide transport, as revealed by selective inhibition.
TLDR
The data indicate that carrier-mediated transport may be essential for termination of the biological effects of anandamide, and may represent a potential drug target.
Biochemistry and pharmacology of arachidonylethanolamide, a putative endogenous cannabinoid.
TLDR
The hypothesis that N-arachidonylethanolamine (AEA), also called anandamide, is synthesized in the brain and functions as an endogenous ligand of the cannabinoid receptor is presented and some evidence to support this hypothesis is explored.
Effect of tetrahydrocannabinols on 3H-acetylcholine biosynthesis in various rat brain slices.
TLDR
The results suggest that the inhibition of ACh synthesis observed in tetrahydrocannabinol-treated rats may be related to interference with the propagated action potential or with the depolarization process in cholinergic neurons.
...
1
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