Polyene antibiotics increase the ionic permeability of synaptosomal plasma membranes.
Biochem Pharmacol
; 41(9): 1345-50, 1991 May 01.
Article
em En
| MEDLINE
| ID: mdl-2018566
ABSTRACT
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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Base de dados:
MEDLINE
Assunto principal:
Polienos
/
Sinaptossomos
/
Candicidina
/
Permeabilidade da Membrana Celular
Limite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
1991
Tipo de documento:
Article
País de afiliação:
Finlândia