Document Detail


Polyene antibiotics increase the ionic permeability of synaptosomal plasma membranes.
MedLine Citation:
PMID:  2018566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of antifungal heptaene antibiotics candicidin and amphotericin B were investigated in isolated cerebral cortical nerve terminals (synaptosomes). The synaptosomes were incubated with candicidin or amphotericin B in the presence or absence of external Ca2+. Candicidin (0.4-0.8 I.U./mL) increased intrasynaptosomal free Ca2+ significantly. This increase was not significantly suppressed by 30 microM verapamil or 2 microM nifedipine. In the absence of extrasynaptosomal Ca2+ intrasynaptosomal free Ca2+ was not changed by candicidin. Amphotericin B increased intrasynaptosomal free Ca2+ as well. Candicidin (0.05-0.6 I.U./mL) increased the respiration rate up to 3.5-fold above the basal rate. This response was not affected by the absence of extracellular Ca2+. Ouabain completely blocked the increase of respiration caused by candicidin, whereas tetrodotoxin was ineffective. The plasma membrane depolarized in a dose-dependent manner after candicidin (0.2-0.8 I.U./mL). The mitochondrial membrane potential was little affected and only at the highest concentrations. The results indicate that heptaene polyenes increase synaptosomal ionic permeability, which is reflected in increased Ca2(+)-influx and accelerated respiration. The increment in synaptosomal free calcium takes place probably as a nonspecific leak via typical polyene-cholesterol channels. The respiration is accelerated by increased Na(+)-permeability through the plasma membrane which stimulates the function of Na+, K(+)-ATPase and thus increases the energy demand.
Authors:
O Raatikainen; R A Kauppinen; H Komulainen; H Taipale; T Pirttilä; J Tuomisto
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  41     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1991 May 
Date Detail:
Created Date:  1991-05-17     Completed Date:  1991-05-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1345-50     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
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MeSH Terms
Descriptor/Qualifier:
Amphotericin B / pharmacology
Animals
Calcium / analysis
Candicidin / pharmacology*
Cell Membrane Permeability / drug effects*
Cerebral Cortex
Cytosol / chemistry
Dose-Response Relationship, Drug
Guinea Pigs
Membrane Potentials
Oxygen Consumption / drug effects
Polyenes / pharmacology*
Synaptosomes / chemistry,  drug effects*
Chemical
Reg. No./Substance:
0/Polyenes; 1397-89-3/Amphotericin B; 1403-17-4/Candicidin; 7440-70-2/Calcium

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


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