F. Vanbambeke et al., ALTERATIONS IN MEMBRANE-PERMEABILITY INDUCED BY AMINOGLYCOSIDE ANTIBIOTICS - STUDIES ON LIPOSOMES AND CULTURED-CELLS, European journal of pharmacology. Molecular pharmacology section, 247(2), 1993, pp. 155-168
Aminoglycoside antibiotics bind to negatively-charged membranes in vit
ro as well as in vivo. We have examined if this binding could be assoc
iated with a change in the properties of membrane permeability. We hav
e used a series of aminoglycoside derivatives and two independent test
systems, namely (i) the release of calcein and of Mn2+ from phosphati
dylinositol-containing large unilamellar vesicles, and (ii) the influx
of Ca2+ into cultured macrophages. We found that certain aminoglycosi
des (e.g., streptomycin, isepamicin) markedly increase the membrane pe
rmeability whereas others (e.g., gentamicin) barely or do not influenc
e it. This increase, when it occurs, is slower or less extensive than
observed with pore-forming agents (mellitin, nystatin) or a Ca2+-ionop
hore (ionomycin). It is not observed with an agent [bis(beta-diethylam
inoethylether)hexestrol] known to cause membrane fusion, and is not as
sociated with any detectable change in membrane fluidity. In computer-
aided conformational analysis of mixed monolayers between phosphatidyl
inositol and the aminoglycosides studied, it was found that those deri
vatives inducing an increase in membrane permeability in our experimen
ts adopted an orientation rather perpendicular to the interface, where
as those with no or only a moderate effect were placed in a parallel o
rientation to this interface. The perpendicular orientation might caus
e a local condition of disorder which could explain the effects observ
ed.