Polyene macrolide antibiotics: indirect stimulation of the Na+/H+ exchanger of BALB/c B lymphoid cell line, A20.
The fluorescent pH probe, 2'-7'-bis (carboxyethyl) 5-carboxyfluorescein, was used to follow changes in internal pH (pHi) induced by aromatic polyene antibiotics in the BALB/c lymphoid cell line A20. The antibiotics studied were vacidin, which contains a free carboxylic group in the position C18 of the macrolide ring, and vacidin glycyl methyl ester and perimycin, which are without free carboxylic groups. Although all of them induced transmembrane Na+ and K+ movements, only vacidin had protonophoric activity, as previously demonstrated for red blood cells [Cybulska B et al., Biochem Pharmacol 38: 1755-1762, 1989]. However, with all three antibiotics, pHi changes were observed in A20 cells. It was demonstrated that the transmembrane H+ movements resulted to different degrees, principally in the case of perimycin and vacidin glycyl methyl ester, or partially in the case of vacidin, from the stimulation of the Na+/H+ exchanger by the induced Na+ permeability. The non-aromatic polyene antibiotic amphotericin B had a low ability to increase proton permeability.
Cybulska
B
B
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, Poland.
Seksek
O
O
Henry-Toulme
N
N
Czerwinski
A
A
Bolard
J
J
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002174:Candicidin / Q000031:analogs & derivatives / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins; D005453:Fluorescence; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D011090:Polyenes / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D005452:Fluoresceins; D011090:Polyenes; D017923:Sodium-Hydrogen Exchangers; D002174:Candicidin; C039465:5-dimethylamiloride; C031985:vacidin A; D000584:Amiloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; C039614:ethylisopropylamiloride