Vesicular ACh transporter

Biosynthesis of ACh involves a reversible reaction in which an acetyl group is transferred from acetyl coenzyme A to choline by the enzyme choline acetyltransferase. The rate-limiting step in ACh s)mthesis is the availability of choline, which is transported into neuronal terminals from the extracellular space by sodium-dependent, high-affinity uptake systems. ACh s)mthesized in the cytosol is stored in vesicles via the action of the vesicular ACh transporter. In response to an action potential, vesicular ACh is released by exocytosis from cholinergic nerve terminals, where it can interact with two major types of receptors muscarinic... 

In addition to the regulation on cholinesterase production, other regulation pathways keep the cholinergic system in balance. For example, acute exposure to anti-ChEs induces brain increases in AChE transcripts accompanied by massive decreases in the vesicular ACh transporter, which together compensate for at least part of the exposure consequences (Kaufer et al., 1998). Also, increased hydrolysis of ACh in AChE-overexpressing transgenic mice was at least partially counterbalanced by a parallel daytime increase in ACh synthesis (Farchi et al., 2003). 

Acethylcholine synthesis and release In the presynaptic cholinergic terminal. Ach, acetylcholine ChAT, choline acetyltransferase VAChT, vesicular acetylcholine transporter AChE, acetylcholineesterase CHT, choline transporter... 

Chakrin and Whittaker (1969) demonstrated that intracerebrally injected or topically applied [Me-3H]choline was rapidly distributed throughout the brain and readily labelled the labile bound and, to a lesser extent, the stable bound (vesicular) ACh. Ansell and Spanner (1968) showed that intracerebrally injected [Me-1 C]-choline was also rapidly phosphorylated and incorporated into a lipid-bound form in whole brain tissue. The rapid utilization of free choline after intracerebral injection contrasts with the more recent finding of Ansell and Spanner (1971) that there is no measurable transport of free choline to the brain from the blood in vivo and that the organ may well receive its supply of choline, and hence the choline for ACh-synthesis, in a lipid-bound form from the blood. 

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