Choline is a selective agonist of α7 nicotnic acetylcholine receptors in the rat brain neurons

In the present study, we demonstrate that choline, a precursor of acetylcholine (ACh) and a product of acetylcholine hydrolysis by acetylcholinesterase (AChE), acts as an efficient and relatively selective agonist of alpha 7-containing nicotinic acetylcholine receptors (nAChR) in neurons cultured from the rat hippocampus, olfactory bulb and thalamus as well as in Pc12 cells. Choline was able to activate postsynaptic and presynaptic alpha 7 nAChRs, with the latter action resulting in the release of other neurotransmitters. Although choline was approximately one order of magnitude less patent than ACh (EC50 of 1.6 mM for choline and 0.13 mM for ACh), it acted as a full agonist at alpha 7 nAChRs. In contrast, choline did not activate alpha 4 beta 2-agonist-bearing nAChRs on hippocampal neurons, and acted as a partial agonist at alpha 3 beta 4-containing nAChRs on PC12 cells. The ethyl alcohol moiety of choline is required for the selective action on alpha 7 nAChR. Exposure of cultured hippocampal neurons for 10 min to choline (10-100 mu M) resulted in desensitization of the native alpha 7 nAChRs, Moreover, chronic exposure (10 days) of the cultured hippocampal neurons to a desensitizing concentration of choline (similar to 30 mu M) decreased their responsiveness to ACh. The selective action of choline on native alpha 7 nAChRs suggests that this naturally occurring compound may act in vivo as an endogenous ligand for these receptors, Putative physiological actions of choline include retrograde messenger activity during the development of the mammalian central nervous system and during periods of elevated synaptic activity that leads to long-term potentiation.