Document Detail

Relationship between inhibition of acetylcholinesterase and response of the rat phrenic nerve-diaphragm preparation to indirect stimulation at higher frequencies.
MedLine Citation:
PMID:  465887     Owner:  NLM     Status:  MEDLINE    
1 Rat isolated diaphragm preparations were stimulated indirectly either intermittently at 20, 50 or 100 Hz or continuously at 0.2 Hz.2 Addition of 1.8 muM paraoxon (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which undergoes slow spontaneous reactivation) for 5 min to the organ bath produced a failure of the muscle to maintain tetanic tension (tetanic fade, Wedensky inhibition) and potentiated the neuromuscular blocking activity of exogenous acetylcholine. The rates of recovery from both these effects were recorded.3 In a series of experiments with dyflos (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which does not undergo spontaneous reactivation) the relationship between functional acetylcholinesterase activity and neuromuscular blocking activity of exogenous acetylcholine was also determined.4 From the data obtained, the relationship between functional acetylcholinesterase activity and tetanic fade was calculated. These calculations show that (i) a considerable reduction in functional acetylcholinesterase activity is required before the diaphragm loses its ability to respond with a sustained tetanus to indirect stimulation at higher frequencies, (ii) the minimum (critical) level of functional acetylcholinesterase activity required for a normal tetanic response is directly related to the frequency of stimulation and (iii) once functional acetylcholinesterase activity has been reduced to the critical level, a very small further reduction leads to a complete tetanic fade.5 The meaning of functional acetylcholinesterase assays and of conclusions which can be drawn from them, is discussed.
P F Heffron; F Hobbiger
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  66     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1979 Jun 
Date Detail:
Created Date:  1979-10-26     Completed Date:  1979-10-26     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  323-9     Citation Subset:  IM    
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MeSH Terms
Cholinesterase Inhibitors*
Diaphragm / physiology*
Electric Stimulation
Isoflurophate / pharmacology
Muscle Contraction / drug effects
Neuromuscular Junction / drug effects,  physiology*
Paraoxon / pharmacology
Phrenic Nerve / physiology*
Reg. No./Substance:
0/Cholinesterase Inhibitors; 311-45-5/Paraoxon; 55-91-4/Isoflurophate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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