Inhibition of multiple molecular forms of human brain acetylcholinesterase by different types of inhibitors.

The inhibition of soluble human AChE and its molecular forms following the electrophoretic separation in polyacrylamide gel to four in vitro inhibitors was studied. Also I50 constants pointing on inhibitory concentration responsible of 50% inhibition have been determined as its negative decade logarithm (pI50). Molecular AChE forms were determined to be of various sensitivity. Those of higher molecular weight showed the maximum sensitivity to the action of all inhibitors used. Of them, the most efficient was O-pinacolyl-methylfluorophosphonate which showed the fluctuation of pI50 values from 9.20 to 6.39. Tacrin was the lesser inhibitor (pI50 values ranging from 5.57 to 3.80). The comparison of mean pl50 values of individual forms with experimentally measured value for AChE without electrophoretic separation pointed on a good correlation. The in vitro inhibition of soluble human brain AChE correlated well with the toxicity of substances tested in vivo in rat. The obtained results are remarquable in that various AChE molecular forms should have a different physiologic functions each, and they confirm the cerebral AChE inhibition is of crucial significance for the toxic effect of various inhibitors.