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Research ArticleArticle

THE ACTION OF PHENYLMETHYLSULFONYL FLUORIDE ON HUMAN ACETYLCHOLINESTERASE, CHYMOTRYPSIN AND TRYPSIN

PAOLA TURINI, SHIGERU KUROOKA, MICHAL STEER, ALDO N. CORBASCIO and THOMAS P. SINGER
Journal of Pharmacology and Experimental Therapeutics May 1969, 167 (1) 98-104;
PAOLA TURINI
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SHIGERU KUROOKA
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MICHAL STEER
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ALDO N. CORBASCIO
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THOMAS P. SINGER
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Abstract

In view of the prevalent clinical impression that acute hemorrhagic pancreatitis involves autodigestion of the pancreas by prematurely activated pancreatic proteolytic enzymes and of reports in the literature that phenylmethylsulfonyl fluoride (PMSF) and related compounds inactivate trypsin and chymotrypsin (from bovine tissues) without affecting acetylcholinesterase (from electriceel), we have studied the action of PMSF on human enzymes and its toxicity in vivo. PMSF rapidly inactivates purified chymotrypsin from human pancreas, although human trypsin is less susceptible to inhibition by PMSF. In contrast to the insensitivity of acetylcholinesterase from electric eels to PMSF, which was confirmed, the enzyme from human erythrocytes is rapidly inhibited by low concentrations of PMSF. This appears to be the first major difference detected between acetylcholinesterases from mammalian sources and from the electric eel. C14-labeled PMSF penetrates human red cells rapidly and inhibits acetylcholinesterase in situ. The labeled inhibitor also penetrates freely through the blood-brain barrier. Despite these suggestions of potential toxicity, PMSF had no discernible effect on synaptic transmission at the neuromuscular junction in the isolated rat diaphragm preparation, and its systemic toxicity when administered to mice i. p. was rather low (LD5O = 200 mg/kg).

Footnotes

    • Received August 5, 1968.
    • Accepted December 11, 1968.
  • © 1969, by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 167, Issue 1
1 May 1969
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Research ArticleArticle

THE ACTION OF PHENYLMETHYLSULFONYL FLUORIDE ON HUMAN ACETYLCHOLINESTERASE, CHYMOTRYPSIN AND TRYPSIN

PAOLA TURINI, SHIGERU KUROOKA, MICHAL STEER, ALDO N. CORBASCIO and THOMAS P. SINGER
Journal of Pharmacology and Experimental Therapeutics May 1, 1969, 167 (1) 98-104;

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Research ArticleArticle

THE ACTION OF PHENYLMETHYLSULFONYL FLUORIDE ON HUMAN ACETYLCHOLINESTERASE, CHYMOTRYPSIN AND TRYPSIN

PAOLA TURINI, SHIGERU KUROOKA, MICHAL STEER, ALDO N. CORBASCIO and THOMAS P. SINGER
Journal of Pharmacology and Experimental Therapeutics May 1, 1969, 167 (1) 98-104;
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