Skau K A, Shipley M T
Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, OH 45267-0004, USA.
Neuropharmacology. 1999 May;38(5):691-8. doi: 10.1016/s0028-3908(98)00205-6.
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.
苯甲基磺酰氟（PMSF）对脑与外周乙酰胆碱酯酶（AChE）的差异性抑制表明，PMSF可能优先抑制不同的AChE分子形式。在全身和体外给予PMSF后检测了AChE抑制情况。全身给药未导致明显的行为变化，但脑AChE活性降低了71%；半膈肌、趾长伸肌和比目鱼肌的AChE活性分别降低了65%、50%和41%。肌肉中的不对称AChE降低程度最大（50 - 80%）。四聚体形式在脑和半膈肌中受到抑制（60 - 76%），但在其他肌肉中未受抑制（18 - 22%）。单体AChE在所有组织中均未受抑制。当将PMSF添加到肌肉匀浆中时，所有形式的AChE均受到同等程度的抑制。纯化的单体和四聚体形式在体外受到同等程度的抑制。这些结果表明，PMSF对AChE的抑制是选择性抑制膜相关形式的结果，且明显的脑选择性与脑中膜相关AChE所占比例较高有关。
