CHOLINE IS A SELECTIVE AGONIST OF ALPHA-7 NICOTNIC ACETYLCHOLINE-RECEPTORS IN THE RAT-BRAIN NEURONS

In the present study, we demonstrate that choline, a precursor of acet ylcholine (ACh) and a product of acetylcholine hydrolysis by acetylcho linesterase (AChE), acts as an efficient and relatively selective agon ist of alpha 7-containing nicotinic acetylcholine receptors (nAChR) in neurons cultured from the rat hippocampus, olfactory bulb and thalamu s as well as in Pc12 cells. Choline was able to activate postsynaptic and presynaptic alpha 7 nAChRs, with the latter action resulting in th e release of other neurotransmitters. Although choline was approximate ly one order of magnitude less patent than ACh (EC50 of 1.6 mM for cho line and 0.13 mM for ACh), it acted as a full agonist at alpha 7 nAChR s. In contrast, choline did not activate alpha 4 beta 2-agonist-bearin g nAChRs on hippocampal neurons, and acted as a partial agonist at alp ha 3 beta 4-containing nAChRs on PC12 cells. The ethyl alcohol moiety of choline is required for the selective action on alpha 7 nAChR. Expo sure 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 d esensitizing concentration of choline (similar to 30 mu M) decreased t heir 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 physiol ogical actions of choline include retrograde messenger activity during the development of the mammalian central nervous system and during pe riods oi elevated synaptic activity that leads to long-term potentiati on.