Abstract
Differential inhibition of brain versus peripheral acetylcholinesterase (AChE) by phenylmethylsulfonyl fluoride (PMSF) suggested that PMSF might preferentially inhibit different AChE molecular forms. AChE inhibition was examined after systemic and in vitro PMSF treatment. Systemic administration resulted in no overt behavioral changes but produced a 71% reduction in brain AChE; hemidiaphragm, extensor digitorum longus and soleus muscles showed 65, 50 and 41% reductions. Muscle asymmetric AChE was reduced to the greatest extent (50–80%). The tetrameric form was inhibited in brain and hemidiaphragm (60–76%) but spared in other muscles (18–22%). Monomeric AChE was spared in all tissues. When PMSF was added to a muscle homogenate all forms were inhibited equally. Purified monomer and tetramer forms were inhibited equally in vitro. These results suggest that PMSF inhibition of AChE is a consequence of a selective inhibition of membrane-associated forms and that the apparent brain selectivity is related to the greater fraction of membrane-associated AChE in brain.
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