CHEMOTHERAPY

CHEMOTHERAPY
1174
Effects
of
aminoglycoside
antibiotics
of
of Biology,
of
The
present
study
was
(AKM)
and
tractile
response
was
deferens
0.5
msec
was
not
of
are
by
response
intramural
nerves
response
pulses
of
tetrodotoxin
was
deferens
in
and
the
was
be
response
and
by
triphosphate.
exceedingly
by
KM,
Key
It
than
words:
nerve
in reducing
nerve
and
RSM
seems
they
are
responses
each
affect
aminoglycoside
effect
stimulation.
both
possible
on
added
the
All
the
general,
metabolized
urine'.
aminoglycoside
in the
Several
body
reports
the
by
the
three
and
at
the
the
nerves
deferens
evoked
g/ml-1 •~
the
response,
was
a
added
10'
contractile
manner.
withmuch
approxi-
treatments,
that
exogenously
about
added
response
a conclusion
muscle
are
is,
mentioned
contractile
and
antibiotics
noranerves
exogenously
bring
these
of
of the
that
concentration
of
may
sympathetic
contractile
these
antibiotics
concerning
muscle
of the
was
on
the
greater
latter.
antibiotics,
and are
presence
the
of
the
rectangular
the
(5 •~ 10-6
reduced,
amplitude
of
on
a concentration-dependent
findings
effects
INTRODUCTION
In
as
noradrenaline
on
intramural
that
was
well
was
contrac-
sympathetic
amplitude
antibiotics
these
the
moreover,
AKM
the
induced
of these
the
g/m1),
in
on
from
as
reduced
in
isolated
of 5 •~ 10g/ml,
exogenously
However,
also
10-3
g/ml)
stimulation
contractile
the
of
but
the
with
5 sec
proposed,
5 Hz)
current
Further,
released
noradrenaline
volt,
above-mentioned
stimulation
been
isolated
supplying
the
current
con-
of
tetrodotoxin,
electrical
of
electrical
has
g/m1-1 •~
10-3
and
the
period
while
added
(1 •~ 10-5
stimulation,
potent
It
nerves
electrical
the
(50
and
stimulation).
simultaneously
at a concentration
of
electrical
AKM
deferens.
are
g/m1-1 •~
each
of
pulses
of
(KM),
onthe
response
guanethidine
nerves,
a
co-transmitters,
electrical
amplitudes
muscle
induced
KM
RSM,
by
kanamycin
contractile
effect
for
effect
of
antibiotics,
intramural
nerve
stimulation).
as
by
stimulus
induced
effects
rectangular
the
duration
exogenously
(5 •~ 10-5
adenosine
former
act
by
a
a stimulus
muscle
electrical
that
to
triphosphate
and
the
deferens
adenosine
induced
mation,
was
due
with
(electrical
50 msec
The
sympathetic
to
was
(electrical
RSM
AKM
due
deferens
the
abolished
Therefore,
was
of
triphosphate.
and
KM,
5 Hz)
response
adenosine
g/ml)
be
isolated
deferens,
contractile
was
Technology,
7, 1993)
aminoglycoside
deferens.
postganglionic
may
may
drenaline
the
was
Medical
Japan
School ** of Medicine.
July
investigate
and
241,
University
stimulation
of 5 sec
hexamethonium.
of the
(50 volt,
pig
electrical
Yokohama
(RSM),
guinea
a period
undoubtly
contractile
tile
by
for
affected
deferens
isolated
induced
duration
to
ribostamycin
response
Koeda**
of Nursing
*
23, 1993•EAccepted
undertaken
contractile
Takemi
Showa
April
the
deferens
College
Asahiku,
Pathology,
(Received
bekanamycin
and
Prefectural
Nakao-cho,
Department
was
Yoshida*
Kanagawa
50-1
on
guinea-pig
Masahide
Laboratory
NOV. 1993
are
not
antibiotics
have
suggested
excreted
intact
in
reduce
the
effects
of
the
on
that
its contractile
effects
deferens
of
organs
they
act
with
response-6).
aminoglycoside
smooth
directly
We
muscle
on muscle
to
investigated
antibiotics
on
the
Aminoglycoside
VOL, 41 NO, 11
smooth
muscle
which
is
nerves,
and
biotics
may
of the
urinary
have
of
not
guinea
the
the
under
the
on
of
on the
smooth
the
the
with
smooth
effects
that
pig
muscle
nerves.
the
pigs
guinated,
stripped
of
segment
from
the
of
an
has
7.3).
and
side of each
exogenously
nously
added
The
betweenthe
trode
was
approximately
was
placed
and
very
The
to
face
sulfate
to
were
are
bath
the
of
and
AKM
and
673 pg/mg,
the
of
the
RSM
in
the
kanamycin
ribostamycin
indicates
potency
the final
given
value
which
antibiotic.
used
714 pg/mg
The
in this
and
exper-
686
pg/mg,
2 mm.
the
preparation
was
pulses
from
0.5-50
The
the
preparation,
msec
for
As
were
adenosine
in
for
a
the
idine
(1 •~ 10
did
the
contractile
2, KM,
the
level
antibiotic
and
of
after.
This
a period
of
concentration
the
of
the
the
con-
and
by
rectangular
all
As
the
on
for
the
was
which
response
g/m1),
in
reduced
That
is to
reached
addition
the
of
same
level
observed
produced
(data
a
shown
immediately
response.
effect
RSM
duration
after
10
on
5 min.
amplitude
remained
g/ml-1 •~
con-
AKM
msec
of
its
of antibiotic
(1 •~ 10-5
0.5
RSM
4 min
contractile
KM,
contractile
of
reducing
Hex-
the
stimulation
induced
of
and
of
RSM
electrical
intervals
reduction
5 Hz)
in
5 Hz)
AKM
shown),
1-2).
affect
and
by
effects
at
Guaneth-
not
(Fig.
not
AKM
response
5 sec
amplitude
did
1-1).
(data
M)
reabol-
1-3).
KM,
induced
observed
maximum
KM
(Fig.
of
response
the
M)
phar-
almost
(Fig.
(3 •~ 10-7
of
contractile
M)
it
dura-
contractile
effects
these
response
with
msec
a
the
abolished
response
Effects
evoked
on
(1 •~ 10-4
(50 volt,
5'-triphosphate
on
electrical
of 0.5
(5 •~ 10-6
M)
of
say,
5 sec
contractile
period
stimu-
and
signifi-
stimulation
5 Hz)
observed
tetrodotoxin
We
Fig.
of
then
pulses
nearly
by
electrical
antagonists
ished
the
1,
Guanethidine
tractile
electrode
SD,
the
induced
(50 volt,
period
We
macological
on
Fig.
pulses
response.
2.
elec-
means •}
evaluate
antagonists
response
shown
rectangular
tractile
other.,
to
pharmacological
contractile
tion
used
of
which
electrically
(50 volt,
Effects
prepa-
one
as
used
differences.
amethonium
pins
each
other
expressed
was
stimulation
electhe
electrodes
and
of
the
recorded
stimulus
with
are
t-test
RESULTS
as
exoge-
near
face
the
force
platinum
is to say,
to
to
a
stimula-
Two
as
preparation
close
and
5 sec.
drugs
used
these
concentration
organ
results
sponses.
response
was
two
testis
and
1 g.
That
rectangular
ranging
pins
placed
between
set
with
thread
used
were
preparation.
space
it.
drugs
(AKM)
of KM,
Student's
tion
4.7
16.3
electrical
of
and
Krebs
the
noradrenaline
were
02
the
mechanical
by
load
x 5 mm)
parallel
silk
an
NaCI,
near
triphosphate
a
placed
with
in the
cance
was
NaH2P04
end
The
added
The
durations
by
electrodes
the
1.4
induced
were
lated
Each
converted
were
tetro-
bekanamycin
bath;
bekanamycin
potencies
solu-
95%
of
was fixed
connected
under
(5 mm
touching
(KM),
1.
as
Krebs
133.5
The
adenosine
isometrically
was
of
organ
Each
used
with
follows:
MgC12,
exan-
preparation
gassed
glucose.
preparation
tion,
ration
the
section.
iment
excised,
was
composition
transducer.
that fixed
in
hexamethonium
hydrochloride,
sulfate.
concentrations
values
deferentia,
containing
and
preparation
was
vasa
Each
as
0.1
and
desheathed.
in length,
The
7.8
displacement
trodes.
and
bath
was
2.5 CaC12,
plates
sulfate,
sulfate,
ribostamycin
The
was
sympa-
were
of the
mm
at 28•Ž
(pH.
of each
tissue
organ
(mM)
end
kanamycin
The
stunned
deferentia
preparation.
in
NaHCO3
other
were
midportion
12-15
tion maintained
KCI,
vasa
the
experimental
CO2
dotoxin,
METHODS
g)
connective
approximately
solution
AND
(300-500
and
immersed
-noradrenaline
(RSM)
rebos-
which
control
guanethidine
(
Results
We,
and
deferens,
salt,
chloride,
respectively.
MATERIALS
The
of
of aminoglycoside
was
is under
effects
1175
disodium
We
nerves.
Guinea
5%
muscle).
on the was deferens
and
nerves
bekanamycin
guinea
muscle
its
sympathetic
(kanamycin,
tamycin)
as
concerning
the
anti-
cholinergic
organs
investigated
antibiotics
aminoglycoside
well
report
control
therefore,
as
any
antibiotics
the
bladder,
parasympathetic
intramural
bladder
found
urinary
of
that
affect
pig
control
suggested
these
thetic
the
under
antibiotics
not
AKM
each
there-
at
any
a reducshown).
(5 •~ 10-6
CHEMOTHERAPY
1176
1
2
NOV,1993
1
2
3
3
Fig. 1. Effects of pharmacological
antagonists
on the contractile response induced by electrical stimulation.
Electrical stimulation was given with rectangular
pulses (50 volt, 5 Hz) of 0.5 msec
duration for a period of 5 sec at intervals of 5
min. 1: Effect of guanethidine
(Gua) , 5 x 10-6
M. 2: Effect of tetrodotoxin
(TTX) , 3 x 10-7
M. 3: Effect of hexamethonium
(Hexa), 1 x
10 M. Electrical stimulation was applied at
the triangular dots. Each agent was given at
the arrow mark.
g/ml-1 x 10-3 g/ml) and RSM (5 x 10-5 g/ml-1 x
10-3 g/ml) significantly reduced the amplitude of
the contractile response in a concentration-dependent manner (Table 1) . The reducing effects of these
antibiotics were restored by washing with normal
Krebs solution for approximately 30 min (Fig. 2).
As shown in Table 1, the reducing effect on the
amplitude of the contractile response was in the
following order: AKM > KM > RSM.
3. Effects of KM, AKM and RSM on the contractile response induced by electrical stimulation
in the presence of tetrodotoxin
First of all, the preparation, in the presence of
tetrodotoxin (3 x 10-7 M) , was electrically stimulated with rectangular pulses (50 volt, 5 Hz) of dura-
Fig. 2. Effects of kanamycin (KM), bekanamycin (AKM) and ribostamycin (RSM) on
the contractile response induced by electrical
stimulation.
Electrical stimulation was given with rectangular pulses (50 volt, 5 Hz) of 0.5 msec
duration for a period of 5 sec at intervals of 5
min. Electrical stimulation was applied at the
triangular dots. 1: Effect of KM, 5 x 10-4g/ml.
2: Effect of AKM, 5 x 10-4 g/ml. 3: Effect of
RSM, 5 x 10-4 g/ml. Each agent (KM, AKM
or RSM) was given at the arrow mark. The
right side shows the contractile response observed 30-40 min after washing with normal
Krebs solution.
tions of 0.5 msec, 5 msec and 50 msec for a period of
5 sec. The preparation showed no response to the
stimulation with rectangular pulses of 0.5 msec
duration, while it showed a very weak contractile
response to the stimulation with rectangular pulses
of 5 msec duration (Fig. 3). The preparation, moreover, showed a remarkable contractile response to
stimulation with rectangular pulses of 50 msec duration (Fig. 3). Then we observed the effects of KM,
AKM and RSM at a concentration of 5 x 10 g/ml
on the contractile response induced by rectangular
pulses (50 volt, 5 Hz) of 50 msec duration for a
period of 5 sec in the presence of tetrodotoxin (3 x
10-7 M). At this concentration, each antibiotic
Aminoglycoside
VOL.41 NO.11
Table
1, Effect
of kanamycin,
response
The
preparation
msec
duration
used.
Each
responses
was
for
value
significance
namely,
from
the
period
differences
control,
at
of the contractile
N
the
from
P<0.05,
pulses
indicates
mean •}
after
SD
addition
on
the
of
value
(50
the
of
P<0.01
response
ribostamycin
rectangular
5 sec.
the
min
and
1177
the contractile
stimulation
with
of
represents
14
on the was deferens
bekanamycin
by electrical
stimulated
a
observed
indicate
reduced the amplitude
induced
antibiotics
the
agent.
before
the
5 Hz)
of
*,
0.5
contractile
* *,
addition
P<0.001,
of
of preparations
amplitudes
an
and
volt,
number
and
of
an
* * *
agent,
respectively.
effects of these antibiotics
were restored
by washing
(Fig. 3 and Table 2-A) . The reducing effects of the
antibiotics were restored by washing with Krebs
with normal Krebs solution for approximately
30
min (Fig. 4) . The reducing effect on the amplitude
solution containing
tetrodotoxin
(3 x 10-7 M) for
approximately 30 min (Fig. 3) . The reducing effect
of the contractile
response was in the following
order: AKM > KM > RSM (Table 2-B).
on the amplitude of the contractile response was in
the following order: AKM > KM > RSM (Table 2-
5.
Effects
of KM, AKM and RSM on the con-
A).
tractile
response
induced
adenosine triphosphate
4. Effects of KM. AKM and RSM on the contractile response induced by exogenously
added
As shown in Fig. 5, the preparation
showed a
contractile
response to exogenously
added adeno-
noradrenaline
sine
As shown in Fig. 4, the preparation
showed a
contractile response to exogenously
added nora-
RSM, each at a concentration
of 5 x 10' g/ml,
reduced its amplitude
(Fig. 5 and Table 2-C). The
drenaline
reducing
(1 x 10
at a concentration
amplitude
M) . KM, AKM and RSM, each
of 5 x 10-4 g/ml,
(Fig. 4 and
Table
2-B).
reduced
The
its
reducing
triphosphate
effects
by exogenously
(5 x 10-5 M) .
KM,
of these antibiotics
AKM
added
and
were restored
by washing with normal Krebs solution for approximately 30 min (Fig. 5). The reducing effect on the
NOV, 1993
CHEMOTHERAPY
1178
1
1
2
2
3
3
4
Fig. 3. Effects of kanamycin
(KM), bekanamycin (AKM) and ribostamycin
(RSM) on
the contractile response induced by electrical
stimulation in the presence of tetrodotoxin.
1: The preparation, in the presence of tetrodotoxin (3 x 10-7 M) , was stimulated
with
rectangular
pulses (50 volt, 5 Hz) of durations of 0.5, 5, and 50 msec (ms) at the triangular dot, as indicated, for a period of 5 sec.
2-4: The preparation, in the presence of tetrodotoxin (3 x 10-7 M), was stimulated
with
rectangular
pulses (50 volt, 5 Hz) of 50 msec
duration at the triangular dots for a period of
5 sec. 2: Effect of KM, 5 x 10-4 g/ml. 3: Effect
of AKM, 5 x 10-4 g/ml. 4: Effect of RSM, 5 x
10 g/ml. The left side in 2-4 shows the
contractile response in the absence of an agent
(KM, AKM or RSM) , namely, the control.
The middle in 2-4
shows the contractile
response in the presence of an agent. Each
agent was given 14 min before electrical stimulation (at the arrow mark). The right side in
2-4 shows the contractile response observed
30-40 min after washing with Krebs solution
containing tetrodotoxin
(3 x 10-7 M).
Fig. 4. Effects of kanamycin
(KM), bekanamycin (AKM) and ribostamycin
(RSM) on
the contractile
response induced by exogenously added noradrenaline.
1: Effect of KM, 5 x 10-4 g/ml. 2: Effect of
AKM, 5 x 10-4 g/ml. 3: Effect of RSM, 5 x 10-4
g/ml. In all experiments,
noradrenaline
(1 x
10-5 M) was given at the triangular dot. Each
agent (KM, AKM or RSM) was given 14 min
before the addition of noradrenaline
(at the
arrow mark). The left side in 1-3 shows the
contractile
response
in the absence of an
agent, namely, the control. The middle in 1
3 shows the contractile
response in the presence of an agent. The right side in 1-3 shows
the contractile response observed 30 min after
washing with normal Krebs solution.
The contractile
response
induced
by
the
electrical
the contractile
the release of transmitter
of the contractile
response was in the
order: AKM > KM > RSM (Table 2-C).
DISCUSSION
Electrical
stimulation
0.5 msec duration
with rectangular
evoked
a contractile
response.
stimulation
response
(Fig. 1).
may be due to
from intramural
postgan-
glionic sympathetic
nerve endings of the preparation as a result of a stimulus effect of the electrical
current
pulses of
in nature,
blocker. Hexamethonium,
a ganglionic blocker, did
not affect the amplitude of the contractile response
Therefore,
amplitude
following
is adrenergic
since it is abolished by guanethidine,
an adrenergic
neuron blocking agent, and tetrodotoxin,
a neuron
on the intramural
nerves of the preparation
(electrical nerve stimulation).
On the other hand,
electrical stimulation with rectangular pulses of 50
Aminoglycoside
VOL.41 NO.11
Table
2.
Effects
of
kanamycin,
response
Effect
of
electrical
M),
a
added
adenosine
responses
indicate
3).
in
blocker,
This
result
is not
mediated
current
on
but
is
by
the
posed,
by
that
nerves
in
noshine
triphosphate
at
That
was
We
is
to
deferens
then
It
and
noradrenaline
the
act
been
-adrenoceptor
they
and
added
was
act
to
of
on
the
the
act,
and
re-
to
muscle7•`9)
muscle
in
the
wall.
observed
RSM
on
the
effects
of
KM,
AKM
and
the
g/ml
to
8 x 10-5
an
the
in
g/ml,
the
smooth
nerves.
AKM
(5 x 10-6
of
electrical
nerve
of
already
of
KM
x
the
these
1.9
and
x
when
control
we
these
x
g/ml-1
10-3
g/ml)
each
in
1).
of
of
not
view
sympag/m1),
and
RSM
reduced
a
KM,
5 x 10-4
a
organs
the
x 10-3
g/ml)
response
(Table
have
on
of
10-5
to
point
antibiotics
the
stimulation
concentration
about
However,
contractile
manner
AKM
known,
(1 x 10-5
10-3
triphos-
KM,
clinical
under
g/ml -1
noradren-
administrated
from
effects
g/ml -1
amplitude
range
dose10•`18).
muscle
thetic
added
intramuscularly
report
preparation
electrical
of
the
as
the
adenosine
concentration
clinical
any
of
stimulation,
added
is
are
a
of
exogenously
blood
antibiotics
at
and
response
highest
in
each
of
nerve
exogenously
The
10-5
of
* *
addition
stimulation,
dependent
the
the
contractile
RSM
(5 x
agent.
electrical
and
with
number
respectively.
by
at
of
amplitudes
an
before
P <0.001,
Effect
exogenously
the
the
of
duration
C:
by
of
value
msec
M).
indicates
concerning
132-purinoceptor
wall,
the
found
ade-
10-5
addition
and
man
sym-
and
deferens
directly
adenosine
co-transmit-
shown
response
the
pro-
from
as
and
of
been
released
the
phate.
preparation
has
N
aline
preparation,
the
tissue,
contractile
say,
of
mean •}SD
muscle
electrical
effect
noradrenaline
the
in
the
muscle
have
al
muscle
mediate
the
the
stimulus
simultaneously
Exogenously
spectively,
direct
of
the
.
by
(3 x10-7
of contractile
induced
M)
induced
response
of
stimulation).
are
ters.").
the
a
(Fig.
contractile
nerves
on
moreover,
pathetic
the
a
response
effect
intramural
muscle
triphosphate
of
that
P<0.01
of 50
(1x
the
after
induced
amplitude
response
from
at
tetrodotoxin,
a contractile
a stimulus
current
(electrical
of
control,
the
noradrenaline
min
response
5 Hz)
on
added
of tetrodotoxin
volt,
agent
represents
14
contractile
(50
each
the contractile
triphosphate
presence
contractile
differences
the
the
(5 x 10
value
observed
from
presence
suggests
mediated
electrical
the
evoked
Each
significance
namely,
of
triphosphate
contractile
* *
of
added
amplitude
of
in
pulses
Effect
exogenously
the
used.
*
B:
on
exogenously
adenosine
amplitude
rectangular
sec.
by
on
preparations
agent,
duration
5
the
ribostamycin
stimulation,
added
preparation,
with
of
agent
on
The
induced
each
neuron
agent
stimulated
period
response
msec
each
and
electrical
and exogenously
stimulation.
was
for
by
1179
on the vas deferens
bekanamycin
induced
noradrenaline
A:
antibiotics
the
induced
by
concentrationAKM
g/ml,
and
RSM,
reduced,
NOV,1993
CHEMOTHERAPY
1180
1
of
the
that
two
reduce
contractile
with
effect
as
of
such
muscle").
and
3
response
of
its
of
electrical
nerve
centration
tude
significantly
that
the
the
intramural
the
muscle
Tables
the
All
that
>
2,
>
otics
addition,
was
may
and
in
possible
greater
they
on
are
on
as shown
the
the
and
possible
greater
bring
RSM
nerves
are
In
conampli-
seems
than
by
lower
are
in
the
such
also
reduction
these
amplitude
of
following
order.
RSM.
AKM
seems
the
nerves
deferens.
these findings
sympathetic
at
It
of
of
reducing
reduced
I).
the
release
all
induced
antibiotics
response
KM
KM,
also
was
1 and
contractile
AKM
It
the
the
in
even
10-4g/ml,
sympathetic
of
nerves
response
these
AKM
contractile
since
potent
(Table
smooth
KM,
the
by
contractile
of
is
the
with
that
endings,
stimulation,
effects
treat-
sympathetic
mediated
5x
three
organs
reduce
nerve
con-
mechanism
is
exceedingly
the
than
the
a
conclusion
both
muscle
of
the
effects
that
on
about
affect
intramural
the
was
of
former
than
K,
Yokota
deferens.
these
they
antibi-
are
on
the
latter.
LITERATURE
1)
Koeda
and
In
with much approximation, the amplitudes of contractile responses induced by the three treatments,
that is, electrical muscle stimulation, exogenously
added noradrenaline
and exogenously
added
adenosine triphosphate (Figs. 3-5 and Table 2).
However, each of these antibiotics at a concentration of 5 x 10-4 g/ml was exceedingly potent in
reducing the amplitude of the contractile response
induced by electrical nerve stimulation (Table 1).
From the above-described results, two possible
mechanisms might explain the effects of KM, AKM
and RSM in reducing the contractile response. One
tissue
were
the
and
of
the
concerning
intramural
the
amplitude
in
the
from
antibiotics
above
possibility
deferens
transmitter
Fig. 5. Effects of kanamycin (KM), bekanamycin (AKM) and ribostamycin (RSM) on
the contractile response induced by exogenously added adenosine triphosphate.
1: Effect of KM, 5 x 10-4 g/ml. 2: Effect of
AKM, 5 x 10-4 g/ml. 3: Effect of RSM, 5 x 10-4
g/ml. In all experiments, adenosine triphosphate (5 x 10-5M) was given at the triangular dot. Each agent (KM, AKM or RSM) was
given 14 min before the addition of adenosine
triphosphate (at the arrow mark). The left
side in 1-3 shows the contractile response in
the absence of an agent, namely, the control.
The middle in 1-3 shows the contractile
response in the presence of each agent. The
right side in 1-3 shows the contractile response observed 30 min after washing with
normal Krebs solution.
on
was
on
other
one
of
previously
antibiotics
act
the
the
be
and
each
This
reported
The
RSM
of
by
to
muscle
amplitude
approximation.
that
the
since
the
induced
supposed
on
response,
much
same
act
reduced
responses
ments
is
directly
antibiotics
tractile
the
mechanisms
antibiotics
its
these
2
possible
these
T,
pharmacology
of
Umezawa,
H.
Handbook
62,
of
Koeda
and
experimental
tamycin.
I.
K:
Pharmacological
New
Nakazawa
Rep.
Vol.
pp.293•`356,
Heidelberg,
U,
Clin.
R.(editors).
pharmacology,
antibiotics.
Shibata
Yamagami
Toxicology
antibiotics.
Hooper,
Berlin,
T,
M:
aminoglycoside
Aminoglycoside
Springer-Verlag,
2)
CITED
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T,
York.
Asaoka
studieson
4: 2489•`2501,
H,
vis-
1970
(in
Japanese)
3)
Aratani
H,
Tanaka
studies
apy
4)
Yamanaka
M,
on
H,
apy
20:
studies
10•`17,
1972
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(Abs.
Y,
on
(Abs.
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Chemother-
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Kono
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in
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kanamycin.
1969
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aminodeoxy
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Aratani
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Hirakawa
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Chemother.
Aminoglycoside
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K:
Pharmacological
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studies
Med.
J.:
on
antibiotics
Tominaga
kanamycin.
1029•`1062,
1959
(in
Yoshida
M,
Koeda
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pig
on
urinary
T:
the
Effects
of
contractile
bladder.
13)
amynoglycoside
response
of
Chemotherapy
33:
J S,
Hogaboom
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Pharmacol.
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of
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1969
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kanamycin
in
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Mikata
Hara
S,
the field
43•`48,
K,
Yanagisawa
Nagahisa
K:
of
urology.
1963
(in
M,
Application
of
S,
Ueno
the field
Chemotherapy
urinary
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88•`
M,
Saito
of
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Applica-
obstetrics
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and
116•`119,
Japanese)
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obstetric
Fujita
H:
kanamycin
Chemotherapy
(Abs.
Arata
aminodeoxy
Chemo-
in
J,
Clinical
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of
gynecology.
1969
5,
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K.
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experience
the field
of
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dermatol-
1969
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on
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cal
in
Japanese)
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Yamaji
K,
Chemotherapy
Sugiyama
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English)
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T,
experiences
infections.
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with
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in
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in
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in
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infection.
(Abs.
80•`84,
English)
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with
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Clinical
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0:
kanamycin
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experience
11
purulent
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Miyoshi
guinea-pig
561•`580,
(in
Mizuno
therapy
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eviand
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that
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to
noradrenaline
92:
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41•`53,
the
co-transmitters
deferens.
Ichikawa
69:
G: Evidence
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are
J
deferens
with
Westfall
kanamycin
11)
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tract
447•`454,
purines
was
Pharmacol.
Burnstock
nerves
drenaline
the
co-transmitter
deferens.
O'Donnell
by
of
J.
A,
sympathetic
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Eur.
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7)
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vistamycin.
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T,
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CHEMOTHERAPY
1182
NOV.1993
モルモット輸精管の収縮反応におよぼすaminoglycoside
吉
田
正
antibioticsの
影響
英
神奈川県立衛生短期大学生物学研究室*
小
枝
武
美
昭和大学医学部病理学教室
Aminoglycoside
antibioticsに属するkanamycin(KM),bekanamycin(AKM)お
びrebostamycin(RSM)の
究した。電気刺激(50
volt,0.5msecの
矩形波にて,5H2の
頻度で5 sec間刺激)に
惹起される輸精管の収縮反応は,guanethidineやtetrodotoxinに
amethoniumの
影響を受けなかった。したがって,輸精管に分布している壁内神経は交感
気的神経刺激)に
volt,50msecの
の神経に対する電流の刺
基因している。また,tetrodotoxin存
矩形波にて,5Hzの
頻度で5sec間
刺激)に
在下で,電
気刺激(50
より惹起される収縮反応は,
電流の輸精管筋に対する直接刺激効果(電
気的筋刺激)に
drenalineとadenosine
精管の交感神経から同時に放出され,組
筋にco-transmitterと
triphosphateは,輸
基因している。さらに,nora-
して作用することが知られているが,外
えても,外来性にadenosine
triphosphateを
(5×10-59/m1∼1×1r39/m1)は,各
々,濃
来性にnomdrenalineを
phosphateの3つ
よびRSM
濃度のKM,AKMお
来性に与えたnoradrenalineお
よびRSMは,
よび外来性に与えたadenosine
起される収縮反応の収縮高に対して,よ
よびRSMは,輸
よびRSMは,各
々,電
気的神経刺激により惹
り明らかな減弱効果を示した。上記の事実より,
精管の壁内交感神経と筋の両者に抑制的影響をおよぼすこ
とが示唆された。その抑制的影響は,後者よりも前者に対して大であった。
*横浜市旭区中尾町50-1
tri-
の処置により惹起される収縮反応の収縮高をほぼ同程度に減弱させた。
しかし,同濃度の各抗生剤,KM,AKMお
KM,AKMお
加
度依存的に電気的神経刺激により惹起される
収縮反応の収縮高を減弱させた。5×10-4g/mlの
気的筋刺激,外
織の
加えても,輸精管標本は収縮反応を示した。
KM(1×10-59/m1∼1×10-39/m1),AKM(5×10-6g/m1∼1×10-3g/m1)お
各々,電
より
より阻止されたが,hex-
神経の節後線維であることは確かであり,上記の収縮反応は,そ
激効果(電
よ
摘出モルモット輸精管の収縮反応におよぼす影響について研

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