PMID: 377291May 1, 1979Paper

Neuroactive drugs inhibit trypsin and outer membrane protein processing in Escherichia coli K-12

Proceedings of the National Academy of Sciences of the United States of America
R C GaydaA Markovitz

Abstract

Previous studies demonstrated that a cloned 2-megadalton (MDal) fragment of Escherichia coli DNA contained the structural gene for major outer membrane protein a (also known as 3b or M2 (40 kDal). The present study demonstrates that M2 is synthesized from a 42-kDal precursor that also is present in the outer membrane. The conversion of the 42-kDal precursor to M2 is inhibited by a number of different local anesthetics (procaine, piperocaine, lidocaine, cocaine), by the neuroactive drug atropine, and by the classical trypsin inhibitors N alpha-tosyllysine chloromethyl ketone (TLCK) and benzamidine. Our kinetic studies demonstrate that the amidase action of pure trypsin is inhibited competitively by the local anesthetics tested (excluding lidocaine) as well as by atropine and neostigmine. A mechanism of action for local anesthetics as well as atropine in E. coli may to be inhibit trypsinlike proteases, in a competitive manner, in the region of the outer membrane. The mechanism of action of these compounds in regulating nerve conduction in man have certain features in common with the mechanism proposed in E. coli.

References

Apr 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·H Inouye, J Beckwith
Mar 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·L L RandallL G Josefsson
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Oct 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·J J LinH C Wu
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Jul 5, 2005·Journal of Bacteriology·Hussain MunavarSusan Gottesman

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Citations

Jan 1, 1983·The International Journal of Biochemistry·I Suominen, P Mäntsälä
Dec 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·C A LeeM H Saier
Apr 15, 1981·Biochemical and Biophysical Research Communications·P Régnier
Mar 28, 1980·Biochemical and Biophysical Research Communications·L M TabeW H Elliott
Mar 1, 1986·Journal of Periodontal Research·T M elAttarJ M Goodson
Feb 13, 2001·Journal of Structural Biology·Y Saijo-HamanoK Oosawa
Aug 24, 1999·European Journal of Anaesthesiology·I BátaiM Tekeres
Feb 1, 1983·Journal of Bacteriology·K R RupprechtC Earhart
Mar 1, 1985·Journal of Bacteriology·G Schmitz, V Braun
Nov 21, 1980·Science·W Wickner

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