Document Detail


Forskolin increases the rate of acetylcholine receptor desensitization at rat soleus endplates.
MedLine Citation:
PMID:  2425358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have studied the function of acetylcholine (AcCho) receptors (AcChoRs) in rat soleus endplates before and after exposing the muscles to forskolin, a potent activator of adenylate cyclase. AcChoR function was tested by recording the membrane depolarization evoked by pulses of ionophoretically applied AcCho. Brief (2 msec) AcCho pulses delivered at 7 Hz evoked constant responses at untreated endplates. In contrast, after 10-100 microM forskolin was added to the bath, responses to similar pulse trains fell by as much as 80% within 1 sec. AcCho sensitivity recovered completely in less than 1 min after the pulses were stopped but fell again when the pulses were resumed. Similarly, longer (1 sec) ionophoretic AcCho pulses evoked roughly constant responses at control endplates, but after forskolin treatment the depolarization fell by one-half within less than 200 msec. These results indicate that forskolin increases the rate at which AcChoRs desensitize when exposed to agonist. Focal extracellular recordings showed that 20-100 microM forskolin also increased the decay rate of miniature endplate currents, indicating that forskolin may decrease AcChoR channel open time. Inhibitors of cAMP phosphodiesterase increased the potency of forskolin. When used alone, these inhibitors had effects similar to those of forskolin but smaller. Patch-clamp experiments indicated that forskolin at 100 microM may also interact with AcChoR channels directly, but at 20 microM this effect is negligible. Therefore, it is likely that the forskolin effects were mediated primarily by increased levels of intracellular cAMP.
Authors:
P Middleton; F Jaramillo; S M Schuetze
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  83     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1986 Jul 
Date Detail:
Created Date:  1986-08-01     Completed Date:  1986-08-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4967-71     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Animals
Cyclic AMP / physiology
Enzyme Activation
Forskolin / pharmacology*
Ion Channels / drug effects*
Kinetics
Motor Endplate / drug effects*,  ultrastructure
Neuromuscular Junction / drug effects*
Phosphorylation
Rats
Receptors, Nicotinic / drug effects*
Chemical
Reg. No./Substance:
0/Ion Channels; 0/Receptors, Nicotinic; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; EC 4.6.1.1/Adenylate Cyclase
Comments/Corrections

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