Vesamicol, an inhibitor of acetylcholine vesicle packaging, increases synaptophysin phosphorylation in rat cortical synaptosomes
Abstract
Vesamicol (AH5183) is an inhibitor (IC50, 50 nM) of acetylcholine (ACh) vesicle packaging. Vesamicol increases the phosphorylation pattern of synaptophysin (p38), identified as a vesicle-specific phosphoprotein involved in vesicle-mediated neurotransmitter release. Percoll fractionation of the rat cortex yielded a cholinergic-enriched synaptosomal Fraction 4. Fraction 4 contained the highest enrichment of cholineacetyl-transferase activity (86 +/- 4.6 mumole AcCh/g protein/hr.) in the Percoll gradient. Fraction 4 demonstrated oxygen consumption (108 +/- 23.4 nmole/mg protein), levels of adenosine triphosphate, ATP, (10.29 +/- 0.45 nmole/mg protein) and adenosine diphosphate, ADP, (10.54 +/- 2.72 nmole/mg protein), energy potential (ATP/[ADP] [Pi], (0.49) phosphate uptake (65-80 nmoles phosphate/mg tissue), 32Pi labelling (130 +/- 12 x 10(5) DPM/mg tissue; 74 +/- 9.8 x 10(2) nmoles phosphate/mg tissue). Synaptophysin was identified by Western blotting and confirmed by qualitative immunoprecipitation. Synaptophysin phosphorylation was confirmed by autoradiograph. Synaptophysin phosphorylation increased (225%) in the presence of vesamicol (ED50, 1 nM) in Fraction 4. Vesamicol (50 nM) and vanadate (54 microM) were compared for thei...Continue Reading
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