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Effect of aluminum chloride on ascending colon of the rat
Pharmacological
Research
Communications,
Vol. 17, No,
12, 1985
1121
EFFECT OF ALUMINUM CHLORIDE ON ASCENDING COLON OF THE RAT F. Javier Department
Alfonso
Alvarez,
of
Pharmacology
University
Carvajal
and Alfonso
and Therapeutics.
of Valladolid.
47011
Received
Velasco
Faculty
of Medicine.
Valladolid.
in final form
2 August
Spain. 1985
Summary Aluminum
chloride
(2.48
motility
of ascending
At concentrations
colon
between
dose-dependent acetylcholine.
x 10 -3 Ml inhibits
x 10 -4 to 1.24 of the
manner
the
Higher
doses
rat.
contractions
attributable
to acidification
more
intense
when the
(3.6
and 4.3
mM) or theobromine
Resting
tension
1.24
x 10 -3 M it
induced
by maximal
x 10 -5 to
2.07
produced
a very
of
medium.
incubation
the
medium (10e4
tended
to be smaller in the presence -8 verapamil (3 x 10 and 10 -7 M).
marked
was not
and 10-3
doses
inhibition
Y).
in a of
that
was
effect
an excess This
low calcium
affected.
inhibited
The inhibiting
contained
of
spontaneous
was
of calcium
inhibiting
(0.6
effect
and 1.0
mM) or
Introduction Aluminum
salts
are employed
and Fordtran, in the
1978)
symptomatic
constipating
and,
an inhibitory
effect
Hurwitz,
1973).
(Hurwitz
and Sheehan,
drugs smooth 1973;
(Hurwitz, muscle
study,
motility the
of their
of diarrhoea
is
produced
is
of aluminum
Aluminum 1971)
treatment
salts,
1971),
ability
on the
to acetylcholine
the
1976).
but
it
colonic
moreover,
constipation, The way this
muscle
gastric
the
response
(Peterson
has been attributed
smooth
cause with
ulcer
to induce
(Editorial, unknown,
interfere
and change
of peptic
and
retention
absorption
of the
(Hava
to
of various
gastrointestinal
and KC1 depolarization
(Hava
and Hurwitz,
1975).
In this of
because
relief
effect
in the
we assess
and contractile
the
effects
response
of aluminum to acetylcholine
chloride in the
on spontaneous ascending
colon
rat.
0031--6989/85/l
21121-07/$03.00/0
@) 1985
The Italian
Pharmacological
Society
1122
Pharmacological
Material Ascending Male
colon
Albino
24 hours study.
of
the
Wistar
before 1971).
(Domer,
to assess
colon
was used
both
cases,
A 1 gram
load
were
registered Polygraph
Acetylcholine
response:
Dose-response
curves
to
(Dmax)
on the with 7B,
a force
to cecum, of
of
acetylcholine
were
producing
maximum effect
of experiments
(Tyrode
the
was
ascending In
containing
a mixture
of 95% 02 and
recording.
displacement
procedure
series
effects
of
various
concentrations
as '% of inhibition'
acetylcholine
(Emax = 100%).
assessed
for
In a second choline
every
Muscular
transducer,
Grass
5mm/min. and expression
drawn,
and the
(Emax)
series
of
of
results:
respective
was determined
the
same composition
in calcium
verapamil medium
in
pH-meter
of aluminum once
the
with
a maximum dose
of
expressed
as '% of
acetylcholine In each
the (Dmax)
preparation
introduced.
(E'max)
effects inhibition' in the only
The preparation
(Dmax)
were
incubated
of
was
(Dmax)
of acetylby another
of
and 4.3
calcium and 10
(3.6 -3
in the
the
first
assessed
and series
and
to maximum dose of = 100%).
in the
nutrient
with
aluminum
solution chloride
was for
minutes. are expressed
as means + S.E.M.
new
administered,
As in were
mM),
M) or
incubation
was again
chloride
of the response new medium (E'max
one modification
assessed
506)
mM)
was substituted
was determined.
of aluminum
were
digit
maximum dose
excess
acetylcholine
1.8
chloride.
solution
but
calcium
to maximum dose
(0.6 and 1.0 mM), theobromine (10e4 -8 -7 and 10 M). After 30 minutes'
new maximum response
Results
The pH (Crison,
nutrient
chloride
response
(3 x 10
of experiments,
five
changes,
of aluminum
experiments the
without
of the
concentration
was determined,
one with
the
striations
adjacent
during
at a speed
in this
to acetylcholine.
with
tissue
for
diagonal
in a 10 ml bath
experimental
and expressed
low
mounted
used
portion
response
fasted
experiment.
In a first the
by its immediately
contractile
was put
were
The distal
were
on a Grass
maximum dose
experiment,
at 37 P C, and bubbled
5% co2.
every
the
cm portions
solution,
FT03C,
portion, motility.
to study
2-3
the
250 and 400 grams,
was identified
spontaneous
Tyrode's contractions
colon
between of
The proximal
used
Vol. 17, No.
and Methods
weighing
beginning
The ascending
Communications,
rat:
rats, the
Research
Statistical
significance
was
12. 1985
Pharmacological
Research
determined
Communications,
by application
of
drugs
used:
Vol. 17, No.
Student's
1123
12, 1985
t test.
Drugs: The following
were
chloride
6 H;,O (Panreac),
(Sigma).
Concentrations
acetylcholine
verapamil in the
chloride
(Sigma),
hydrochloride
text
refer
(Knoll)
to final
aluminum
and theobromine
concentrations
in the
bath. Results Effects
on spontaneous
Low concentrations
motility:
(fig.
motility.
Higher
amplitude
of contractions,
1, above)
concentrations but
inhibition
of spontaneous
Effects
on resting
tension:
colon.
chloride
Effects
on the
Aluminum
-3
l),
medium
way, was low
of aluminum
shown)
an
ascending
at high
doses.
the
contractions
manner, 1).
a marked
of
an excess more
High
doses
inhibition,
acidification of
intensely,
this
medium. or theobromine and in a
However,
verapamil
(over
but
the
calcium
acetylcholine.
or contained
tended
of the
effect
(Table
produced
of the
in calcium
and produced
tension
relaxing
inhibited
effect
chloride
resting
contained
chloride
the
frequency
the
to acetylcholine:
to the
solution
aluminum
significant
the
of acetylcholine
not
spontaneous
increased
in a dose-dependent
to be related
nutrient
their
a mild
response
inhibited,
M, data
seemed
When the (Tabie
contractile
seem to affect
motility.
affect
by maximum doses
x 10
effect
not
we observed
chloride
induced 2.48
did
Occasionally
not
1, below:,
reduced
initial
Aluminum
did
(fig.
(Table
when the
l),
the
effect
to be smaller. Discussion
Aluminum
chloride
ascending
colon
resting
tension
stomach
of
Aluminum (Table
inhibits
the
of the
was larger
rat
(fig.
nor produce rat
chloride 1).
spontaneous
(Hava
The inhibition in the
colon
1).
However,
relaxation,
unlike
and Hurwitz,
inhibits
the
1973;
contractions
of the than
motility
contractile
in the
stomach
of the it
does
isolated not
observations
affect in the
Alvarez
et al.,
induced
by acetylcholine
response of the
1983).
to acetylcholine rat
(Alvarez
et al.,
1124
Pharmacological
Research
Communications,
Vol. 17, No.
h
X P
12. 1985
response
Number
Results
verapamil
verapamil
6.87
7.71
- 13.04
-
-
rat.
-+ 1.42 +- 2.29
-+ 1.79 +- 1.98
+- 1.43 +- 3.11
-+ 1.21 -+ 1.79
C
the
chloride
1.76
1.20
1.20
3.73
7.61
7.91
9.56 9.60
3.93
2.07
-+ 0.70a -+ 0.87
-+ 1.64 -+ 0.73a
-+ l.OOa +- 1.06a
-+ 0.97 -+ 2.20a -+ 1.75a
x 10
-5
on contractile
induced
by maximum
2.98
2.53
4.01
4.40
9.26
9.32
14.35 11.06
4.08
-+ 0.77 -+ 1.09
-+ 1.24 -+ 1.81
-+ 2.01a -+ 1.04b
-+ 0.94 -+ 2.53b -+ 1.97b
4.85
4.84
5.08
7.14
11.60
11.52
16.76 14.69
7.59
+- 0.30 +- 1.65
+- 1.46 +- 0.85
+- 1.79 +- 1.04a
-+ 1.80 -+ 2.80a -+ 2.2ga
ALUMINUM CHLORIDE (M) -5 -4 4.14 x 10 1.24 x 10
response
6.53
6.59
6.55
.15.81 8.46
11.48
16.29
10.89 16.35
4.14
doses
1.42a
1.50a 1.64
1.64
1.52a
14.61
16.06
15.03
30.09 13.73
18.12
19.17
14.16 22.28
1.81b
1.24
1.20
-4
acetylcholine
+- 1.06a -+ l.Oga
+ + + + -+ + -+
x 10
of
-3
2.71
3.81b 2.19
1.81
+- 3.07 +- 3.02
+ ++ +-
+ 2.13 + 3.08a +- 2.00
x 10
on
to acetylcholine
obtained
in a normal
medium
(100%)
and in a medium
with
modifications.
as means +- S.E.M., and express the '% of inhibition' of maximum response to acetylcholine. of experimens between 7 and 10. a= p< 0.01, b= pcO.05. C, shows the difference (%) between the maximum
are given
3x10 -8M -7 10 M
mM
0.6
3.73
calcium
-
mM
1.0
calcium
7.26
+ 10.89
6.34
10 -3 M - 13.39
mM
+
theobromine
4.3
calcium
mM
of
10 -4 M -
3.6
calcium
mM
... 0
colon
of aluminum
theobromine
1.8
with
calcium
" Tyrode
NUTRIENT MEDIUM
ascending
TABLE 1: Effect
$ s iit t?
.Ti
g
9 2. 3 2. E .9 C
:
1126
Pharmacological
1983),
under
similar
maximum doses This smooth not
effect
muscle
line
might
of aluminum change
of peristaltic
allow
which
colon
that
both
the
principal
1980;
inhibiting
one or the
inhibitory
effect
would
is
of contractions
If this
Vol. 17. No.
in both
contractility
of motor
explain,
affected
Fontaine
other
at least
12, 1985
cases
et
activities
which
knowing
colonic .lormally
that
responses
al.,
it
1984)
do
acetylcho-
excitatory
is
of
likely
The consecuen-
are however activity
the
the
Our results
to be affected.
peristaltic
in part,
activity
but
in the
are going
on the
of
activities.
mediators
(Bowman and Rand, types
on the
pattern
of activity
ces of the
and using
and non-propulsive
type
is one of the
the
conditions
Communications,
of acetylcholine.
inhibitory
consists
experimental
Research
antagonistic.
were
predominant
constipant
effect
the
of
of aluminum
salts. It
is known
that
aluminum
Hurwitz,
1974;
1975).
when the
variations
of calcium
available
for
(Bolton,
1979),
calcium 1984),
of aluminum (Hurwitz and the
of aluminum
is
becomes
action
marked.
(Table
medium
increase
(Rail,
However, 1980) is
calcium
results
contractions,as
available slightly
nutrient
or theobromine
and Weissinger, calcium
by our
in the
muscular
is more
with
supported
introduced
of calcium effect
interferes
This
in a medium 1980),
when the
or contains
disminished,
the
medium verapamil
the
inhibiting
(Hava 1).
and
Thus,
the
amount
with
excess
inhibiting is
low
in
(Godfraind, effect
lower. Acknowledgments
We wish
to express
particular
thanks
to
Sara Meriel
for
her
technical
help.
References ALVAREZ, F.J., CARVAJAL, A. y VELASCO; A. (1983). V Jornadas Toxicologicas Nacionales. Libro de Actas, Madrid, pp. 137. BOLTON, T.B. (1979). Physiol. Rev., 59: 606-718. BOWMAN, W.C. and RAND, M.J. (1980). %, Textbook of Pharmacology. Bowman, W.C. and Rand, M.J. (Eds.), Blackwell Scientific Publications, Oxford,2nd Ed., PP. 25.29-25.38. DOMER, F.R. (1971). In, Animal Experiments in Pharmacological Analysis. Domer, F.R. (ED.), Charles C. Thomas, Springfield, pp. 223-274. EDITORIAL (1976). N. Eng. J. Med., 294: 218. FONTAINE, J., GRIVEGNEE, A. and REUSE, J. (1984). Br. J. Pharmac., 81: 231-243. GODFRAIND, T. (1984). In, Calcium Entry Blockers in Cardiovascular and Cerebral dysfunctions. Godfraind, T., Herman, A. and Wellens, D. (Eds.), Martinus Nijhoff Publishers, The Hague, pp. 9-18. HAVA, M. and HURWITZ, A. (1973). Europ. J. Pharmacol., 22: 156-161. HAVA, M. and HURWITZ, A. (1974). Arch. Int. Pharmacodyn, 212: 24-31. -
Pharmacological
Research
Communications,
Vol. 17. No.
12. 1985
HAVA, M. and HURWITZ, A. (1975). arch. Int. Pharmacodyn., 214: 213-223. HURWITZ, A. (1971). J. Pharmacol. Exptl. Therap., 179: 485-489. HURWITZ, A. and SHEEHAN, M. (1971). J. Pharmacol Eql. Therap., 179: 124-131. HURWITZ, L. and WEISSINGER, J. (1980). J. Pharmacol. Exptl. Therap., -214: 581-588. PETERSON, W. and FORDTRAN, J. (1978). In, Gastrointestinal Diseases: Phatophysiology, Diagnosis and Management. Sleisinger, M.H. and Fordtran, J. (Eds.), W.B. Saunders Co., Philadhelphia, pp. 801-890. RALL, T.W. (1980). In. The Pharmacological Basis of Therapeutics. Goodman, A., Goodman, L.S. and Gilman, A. (Eds.), Macmillan Publishing co. ( New York, 6th Ed., pp. 592-607.
1127
Research
Communications,
Vol. 17, No,
12, 1985
1121
EFFECT OF ALUMINUM CHLORIDE ON ASCENDING COLON OF THE RAT F. Javier Department
Alfonso
Alvarez,
of
Pharmacology
University
Carvajal
and Alfonso
and Therapeutics.
of Valladolid.
47011
Received
Velasco
Faculty
of Medicine.
Valladolid.
in final form
2 August
Spain. 1985
Summary Aluminum
chloride
(2.48
motility
of ascending
At concentrations
colon
between
dose-dependent acetylcholine.
x 10 -3 Ml inhibits
x 10 -4 to 1.24 of the
manner
the
Higher
doses
rat.
contractions
attributable
to acidification
more
intense
when the
(3.6
and 4.3
mM) or theobromine
Resting
tension
1.24
x 10 -3 M it
induced
by maximal
x 10 -5 to
2.07
produced
a very
of
medium.
incubation
the
medium (10e4
tended
to be smaller in the presence -8 verapamil (3 x 10 and 10 -7 M).
marked
was not
and 10-3
doses
inhibition
Y).
in a of
that
was
effect
an excess This
low calcium
affected.
inhibited
The inhibiting
contained
of
spontaneous
was
of calcium
inhibiting
(0.6
effect
and 1.0
mM) or
Introduction Aluminum
salts
are employed
and Fordtran, in the
1978)
symptomatic
constipating
and,
an inhibitory
effect
Hurwitz,
1973).
(Hurwitz
and Sheehan,
drugs smooth 1973;
(Hurwitz, muscle
study,
motility the
of their
of diarrhoea
is
produced
is
of aluminum
Aluminum 1971)
treatment
salts,
1971),
ability
on the
to acetylcholine
the
1976).
but
it
colonic
moreover,
constipation, The way this
muscle
gastric
the
response
(Peterson
has been attributed
smooth
cause with
ulcer
to induce
(Editorial, unknown,
interfere
and change
of peptic
and
retention
absorption
of the
(Hava
to
of various
gastrointestinal
and KC1 depolarization
(Hava
and Hurwitz,
1975).
In this of
because
relief
effect
in the
we assess
and contractile
the
effects
response
of aluminum to acetylcholine
chloride in the
on spontaneous ascending
colon
rat.
0031--6989/85/l
21121-07/$03.00/0
@) 1985
The Italian
Pharmacological
Society
1122
Pharmacological
Material Ascending Male
colon
Albino
24 hours study.
of
the
Wistar
before 1971).
(Domer,
to assess
colon
was used
both
cases,
A 1 gram
load
were
registered Polygraph
Acetylcholine
response:
Dose-response
curves
to
(Dmax)
on the with 7B,
a force
to cecum, of
of
acetylcholine
were
producing
maximum effect
of experiments
(Tyrode
the
was
ascending In
containing
a mixture
of 95% 02 and
recording.
displacement
procedure
series
effects
of
various
concentrations
as '% of inhibition'
acetylcholine
(Emax = 100%).
assessed
for
In a second choline
every
Muscular
transducer,
Grass
5mm/min. and expression
drawn,
and the
(Emax)
series
of
of
results:
respective
was determined
the
same composition
in calcium
verapamil medium
in
pH-meter
of aluminum once
the
with
a maximum dose
of
expressed
as '% of
acetylcholine In each
the (Dmax)
preparation
introduced.
(E'max)
effects inhibition' in the only
The preparation
(Dmax)
were
incubated
of
was
(Dmax)
of acetylby another
of
and 4.3
calcium and 10
(3.6 -3
in the
the
first
assessed
and series
and
to maximum dose of = 100%).
in the
nutrient
with
aluminum
solution chloride
was for
minutes. are expressed
as means + S.E.M.
new
administered,
As in were
mM),
M) or
incubation
was again
chloride
of the response new medium (E'max
one modification
assessed
506)
mM)
was substituted
was determined.
of aluminum
were
digit
maximum dose
excess
acetylcholine
1.8
chloride.
solution
but
calcium
to maximum dose
(0.6 and 1.0 mM), theobromine (10e4 -8 -7 and 10 M). After 30 minutes'
new maximum response
Results
The pH (Crison,
nutrient
chloride
response
(3 x 10
of experiments,
five
changes,
of aluminum
experiments the
without
of the
concentration
was determined,
one with
the
striations
adjacent
during
at a speed
in this
to acetylcholine.
with
tissue
for
diagonal
in a 10 ml bath
experimental
and expressed
low
mounted
used
portion
response
fasted
experiment.
In a first the
by its immediately
contractile
was put
were
The distal
were
on a Grass
maximum dose
experiment,
at 37 P C, and bubbled
5% co2.
every
the
cm portions
solution,
FT03C,
portion, motility.
to study
2-3
the
250 and 400 grams,
was identified
spontaneous
Tyrode's contractions
colon
between of
The proximal
used
Vol. 17, No.
and Methods
weighing
beginning
The ascending
Communications,
rat:
rats, the
Research
Statistical
significance
was
12. 1985
Pharmacological
Research
determined
Communications,
by application
of
drugs
used:
Vol. 17, No.
Student's
1123
12, 1985
t test.
Drugs: The following
were
chloride
6 H;,O (Panreac),
(Sigma).
Concentrations
acetylcholine
verapamil in the
chloride
(Sigma),
hydrochloride
text
refer
(Knoll)
to final
aluminum
and theobromine
concentrations
in the
bath. Results Effects
on spontaneous
Low concentrations
motility:
(fig.
motility.
Higher
amplitude
of contractions,
1, above)
concentrations but
inhibition
of spontaneous
Effects
on resting
tension:
colon.
chloride
Effects
on the
Aluminum
-3
l),
medium
way, was low
of aluminum
shown)
an
ascending
at high
doses.
the
contractions
manner, 1).
a marked
of
an excess more
High
doses
inhibition,
acidification of
intensely,
this
medium. or theobromine and in a
However,
verapamil
(over
but
the
calcium
acetylcholine.
or contained
tended
of the
effect
(Table
produced
of the
in calcium
and produced
tension
relaxing
inhibited
effect
chloride
resting
contained
chloride
the
frequency
the
to acetylcholine:
to the
solution
aluminum
significant
the
of acetylcholine
not
spontaneous
increased
in a dose-dependent
to be related
nutrient
their
a mild
response
inhibited,
M, data
seemed
When the (Tabie
contractile
seem to affect
motility.
affect
by maximum doses
x 10
effect
not
we observed
chloride
induced 2.48
did
Occasionally
not
1, below:,
reduced
initial
Aluminum
did
(fig.
(Table
when the
l),
the
effect
to be smaller. Discussion
Aluminum
chloride
ascending
colon
resting
tension
stomach
of
Aluminum (Table
inhibits
the
of the
was larger
rat
(fig.
nor produce rat
chloride 1).
spontaneous
(Hava
The inhibition in the
colon
1).
However,
relaxation,
unlike
and Hurwitz,
inhibits
the
1973;
contractions
of the than
motility
contractile
in the
stomach
of the it
does
isolated not
observations
affect in the
Alvarez
et al.,
induced
by acetylcholine
response of the
1983).
to acetylcholine rat
(Alvarez
et al.,
1124
Pharmacological
Research
Communications,
Vol. 17, No.
h
X P
12. 1985
response
Number
Results
verapamil
verapamil
6.87
7.71
- 13.04
-
-
rat.
-+ 1.42 +- 2.29
-+ 1.79 +- 1.98
+- 1.43 +- 3.11
-+ 1.21 -+ 1.79
C
the
chloride
1.76
1.20
1.20
3.73
7.61
7.91
9.56 9.60
3.93
2.07
-+ 0.70a -+ 0.87
-+ 1.64 -+ 0.73a
-+ l.OOa +- 1.06a
-+ 0.97 -+ 2.20a -+ 1.75a
x 10
-5
on contractile
induced
by maximum
2.98
2.53
4.01
4.40
9.26
9.32
14.35 11.06
4.08
-+ 0.77 -+ 1.09
-+ 1.24 -+ 1.81
-+ 2.01a -+ 1.04b
-+ 0.94 -+ 2.53b -+ 1.97b
4.85
4.84
5.08
7.14
11.60
11.52
16.76 14.69
7.59
+- 0.30 +- 1.65
+- 1.46 +- 0.85
+- 1.79 +- 1.04a
-+ 1.80 -+ 2.80a -+ 2.2ga
ALUMINUM CHLORIDE (M) -5 -4 4.14 x 10 1.24 x 10
response
6.53
6.59
6.55
.15.81 8.46
11.48
16.29
10.89 16.35
4.14
doses
1.42a
1.50a 1.64
1.64
1.52a
14.61
16.06
15.03
30.09 13.73
18.12
19.17
14.16 22.28
1.81b
1.24
1.20
-4
acetylcholine
+- 1.06a -+ l.Oga
+ + + + -+ + -+
x 10
of
-3
2.71
3.81b 2.19
1.81
+- 3.07 +- 3.02
+ ++ +-
+ 2.13 + 3.08a +- 2.00
x 10
on
to acetylcholine
obtained
in a normal
medium
(100%)
and in a medium
with
modifications.
as means +- S.E.M., and express the '% of inhibition' of maximum response to acetylcholine. of experimens between 7 and 10. a= p< 0.01, b= pcO.05. C, shows the difference (%) between the maximum
are given
3x10 -8M -7 10 M
mM
0.6
3.73
calcium
-
mM
1.0
calcium
7.26
+ 10.89
6.34
10 -3 M - 13.39
mM
+
theobromine
4.3
calcium
mM
of
10 -4 M -
3.6
calcium
mM
... 0
colon
of aluminum
theobromine
1.8
with
calcium
" Tyrode
NUTRIENT MEDIUM
ascending
TABLE 1: Effect
$ s iit t?
.Ti
g
9 2. 3 2. E .9 C
:
1126
Pharmacological
1983),
under
similar
maximum doses This smooth not
effect
muscle
line
might
of aluminum change
of peristaltic
allow
which
colon
that
both
the
principal
1980;
inhibiting
one or the
inhibitory
effect
would
is
of contractions
If this
Vol. 17. No.
in both
contractility
of motor
explain,
affected
Fontaine
other
at least
12, 1985
cases
et
activities
which
knowing
colonic .lormally
that
responses
al.,
it
1984)
do
acetylcho-
excitatory
is
of
likely
The consecuen-
are however activity
the
the
Our results
to be affected.
peristaltic
in part,
activity
but
in the
are going
on the
of
activities.
mediators
(Bowman and Rand, types
on the
pattern
of activity
ces of the
and using
and non-propulsive
type
is one of the
the
conditions
Communications,
of acetylcholine.
inhibitory
consists
experimental
Research
antagonistic.
were
predominant
constipant
effect
the
of
of aluminum
salts. It
is known
that
aluminum
Hurwitz,
1974;
1975).
when the
variations
of calcium
available
for
(Bolton,
1979),
calcium 1984),
of aluminum (Hurwitz and the
of aluminum
is
becomes
action
marked.
(Table
medium
increase
(Rail,
However, 1980) is
calcium
results
contractions,as
available slightly
nutrient
or theobromine
and Weissinger, calcium
by our
in the
muscular
is more
with
supported
introduced
of calcium effect
interferes
This
in a medium 1980),
when the
or contains
disminished,
the
medium verapamil
the
inhibiting
(Hava 1).
and
Thus,
the
amount
with
excess
inhibiting is
low
in
(Godfraind, effect
lower. Acknowledgments
We wish
to express
particular
thanks
to
Sara Meriel
for
her
technical
help.
References ALVAREZ, F.J., CARVAJAL, A. y VELASCO; A. (1983). V Jornadas Toxicologicas Nacionales. Libro de Actas, Madrid, pp. 137. BOLTON, T.B. (1979). Physiol. Rev., 59: 606-718. BOWMAN, W.C. and RAND, M.J. (1980). %, Textbook of Pharmacology. Bowman, W.C. and Rand, M.J. (Eds.), Blackwell Scientific Publications, Oxford,2nd Ed., PP. 25.29-25.38. DOMER, F.R. (1971). In, Animal Experiments in Pharmacological Analysis. Domer, F.R. (ED.), Charles C. Thomas, Springfield, pp. 223-274. EDITORIAL (1976). N. Eng. J. Med., 294: 218. FONTAINE, J., GRIVEGNEE, A. and REUSE, J. (1984). Br. J. Pharmac., 81: 231-243. GODFRAIND, T. (1984). In, Calcium Entry Blockers in Cardiovascular and Cerebral dysfunctions. Godfraind, T., Herman, A. and Wellens, D. (Eds.), Martinus Nijhoff Publishers, The Hague, pp. 9-18. HAVA, M. and HURWITZ, A. (1973). Europ. J. Pharmacol., 22: 156-161. HAVA, M. and HURWITZ, A. (1974). Arch. Int. Pharmacodyn, 212: 24-31. -
Pharmacological
Research
Communications,
Vol. 17. No.
12. 1985
HAVA, M. and HURWITZ, A. (1975). arch. Int. Pharmacodyn., 214: 213-223. HURWITZ, A. (1971). J. Pharmacol. Exptl. Therap., 179: 485-489. HURWITZ, A. and SHEEHAN, M. (1971). J. Pharmacol Eql. Therap., 179: 124-131. HURWITZ, L. and WEISSINGER, J. (1980). J. Pharmacol. Exptl. Therap., -214: 581-588. PETERSON, W. and FORDTRAN, J. (1978). In, Gastrointestinal Diseases: Phatophysiology, Diagnosis and Management. Sleisinger, M.H. and Fordtran, J. (Eds.), W.B. Saunders Co., Philadhelphia, pp. 801-890. RALL, T.W. (1980). In. The Pharmacological Basis of Therapeutics. Goodman, A., Goodman, L.S. and Gilman, A. (Eds.), Macmillan Publishing co. ( New York, 6th Ed., pp. 592-607.
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