Vesamicol cholinergic

Transmitter storage Vesamicol Cholinergic terminals vesicles Prevents storage, depletes... 

Schematic illustration of a generalized cholinergic junction (not to scale). Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT). This transporter can be inhibited by hemicholinium drugs. In the cytoplasm, acetylcholine is synthesized from choline and acetyl -A (AcCoA) by the enzyme choline acetyltransferase (ChAT). Acetylcholine is then transported into the storage vesicle by a second carrier, the vesicle-associated transporter (VAT), which can be inhibited by vesamicol. Peptides (P), adenosine triphosphate (ATP), and proteoglycan are also stored in the vesicle. Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft (see text). This step can he blocked by botulinum toxin. Acetylcholine s action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending modulate transmitter release. SNAPs, synaptosome-associated proteins VAMPs, vesicle-associated membrane proteins.

The widespread presence of nicotinic receptors in the central nervous system coupled with the relative rarity of a classical synaptic role means that it is still difficult to describe a clear physiological role for these receptors. This is particularly true for receptors in presynaptic locations, for which the level and temporal pattern of exposure to the neurotransmitter are unknown. Approaches that are casting light on this problem include mouse knockout models and transmitter depletion by blockers of vesicular transport processes such as vesamicol the combination of these techniques has recently shown that normal evoked dopamine release in striatal slices is strongly dependent on endogenous cholinergic mechanisms that involve the activation of j32-containing nicotinic receptors (240). 

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