| Polyene antibiotics increase the ionic permeability of synaptosomal plasma membranes. | |
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MedLine Citation:
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PMID: 2018566 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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O Raatikainen; R A Kauppinen; H Komulainen; H Taipale; T Pirttilä; J Tuomisto |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical pharmacology Volume: 41 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1991 May |
Date Detail:
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Created Date: 1991-05-17 Completed Date: 1991-05-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1345-50 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Chemistry, University of Kuopio, Finland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amphotericin B
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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:
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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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