Recent studies suggest that the antifungal agents
itraconazole, bifonazole, and ketoconazole affect calcium-mediated
signal transduction in Trichophyton rubrum. We
have now examined the effects of azole-antifungal agents on
cell membrane function in
T. rubrum, by analysing the effects of itraconazole,
bifonazole, ketoconazole, and lanoconazole on ionomycin-induced
changes in intracellular calcium concentration
([Ca2+]i).
Addition of 1 μm ionomycin to the culture medium
produced a persistent increase in
[Ca2+]i.
While treatment with 1·5–15 nM of
lanoconazole or bifonazole for 24 h did not affect this
ionomycin-induced increase in
[Ca2+]i, 30 nM of these
agents resulted in a transient increase in
[Ca2+]i rather than the usual
sustained increase in [Ca2+]i. This
transient ionomycin-induced increase in
[Ca2+]i was also observed after
treatment with only 1·5 and 3 nM of
ketoconazole or itraconazole. Incubation in the presence of
lanoconazole or bifonazole at [ges ]150 nM, and
ketoconazole or itraconazole at [ges ]15 nM
inhibited both the persistent and transient ionomycin-induced
increase in [Ca2+]i. On the basis
of these findings, it is suggested that
azole antifungal agents disturb membrane function in
T. rubrum, and that one manifestation of this effect
is the disruption of the ionomycin-induced increase in
[Ca2+]i. We report that the
ionomycin-induced increase in
[Ca2+]i is more sensitive to low
concentrations of ketoconazole and itraconazole compared
to bifonazole and lanoconazole.