Choline analogues: their use in studies of acetylcholine synthesis, storage, and release.
The objective of this article is to illustrate how choline analogues might provide insight into mechanisms that regulate the synthesis, storage, and release of acetylcholine (ACh). Studies with false neurotransmitters provide information about the origin of releasable transmitter. Thus, false esters that distribute like ACh to vesicle-bound stores are as releasable as is ACh, but esters that poorly localize to synaptic vesicles are poorly releasable. Studies of choline analogue uptake provide information about the structural specificity of that transport process and, also, show that choline uptake is regulated in response to activity. Thus, stimuli that normally release transmitter increase the rate of choline transport, presumably to provide more precursor for ACh synthesis. However, the relationship between precursor delivery and product formed can be dissociated, suggesting that some factor in addition to choline delivery is involved in ACh synthesis regulation. Studies with a compound (AH5183), which inhibits ACh uptake by synaptic vesicles, provide information about the relationship of ACh stores and releasable transmitter. In the presence of AH5183 some 15% of nerve terminal ACh is released in response to nerve impulses, suggesting the existence of a small population of vesicles that contain readily releasable ACh. In presence of AH5183, ACh synthesis is activated even when ACh release is depressed, showing that transmitter synthesis can be regulated by some factor other than nerve terminal ACh levels.
D000107:Acetylation; D000109:Acetylcholine / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000502:physiology; D004558:Electric Stimulation; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism
D002795:Choline O-Acetyltransferase; D002794:Choline; D000109:Acetylcholine; D002118:Calcium