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Abstract
In the present work, 112 adult male rats were divided into 14
groups, 8 animals each, weighing 200-250 mg. Rats were
anaesthetized with urethane (600 mg/kg) injected intraperitonealy
(ip). A midline abdominal incision was done in the skin. Gut segments
were sequentially positioned to facilitate the implantation of
microelectrodes. In the stomach, the microelectrodes were glutted
onto the serosa of the gastric antrum, ~2 cm proximal to the pyloric
sphincter. In the duodenum, the microelectrodes were glutted onto the
anti-mesenteric border of the duodenum, ~2 cm distal to the
gastroduodenal junction, whereas, in the proximal colon the
microelectrodes were glutted onto the anti-mesenteric border of the
proximal colon, ~2 cm distal from the ileo-colonic junction.
Antral, duodenal and proximal colonic motility and the
sympathetic nerve activity were recorded by the physiograph ‛
Washington 400 MD4C Oscillograph’ Bioscience, Sheerness. Kent.
UK.
Assessment of the Gastrointestinal Response to Dopamine
Injection.
Experiment I: In this experiment three groups (Groups 1, 2 and 3)
of rats were used to assess the effect of subcutaneous dopamine
injection at a dose of 0.01 (Group 1), 0.1 (Group 2) and 1 mg/kg
(Group 3) on amplitude, frequency and motility index of antral,duodenal and proximal colonic motility respectively. These
parameters were recorded before (control) and at 5, 15, 30, 60 and 90
min post-injection of dopamine.
Results obtained from this experiment revealed that, subcutaneous
(sc) injection of dopamine as low as 0.01 mg/kg induced a nonsignificant
decrease in the mean levels of amplitude, frequency and
motility index of antral, duodenal and proximal colonic contractions.
Subcutaneous injection of dopamine at a dose of 0.1 mg/kg caused a
significant decrease in the mean levels of amplitude, frequency and
motility indexes of antral, duodenal and proximal colonic contractions
at 5, 15 and, 30 min post-injection of dopamine. At 60 min postinjection
the values which were changed by dopamine injection
tended to return to baseline levels. Subcutaneous injection of
dopamine at a dose of 1 mg/kg resulted in a significant decrease in the
mean levels of amplitude, frequency and motility indexes of antral
duodenal and proximal colonic contractions at 5, 15, 30, and 60 min
after dopamine injection. At 90 min post-injection the values which
were changed by dopamine injection tended to return to the baseline
levels.
Experiment II: In this experiment two groups of rats were used to
further confirm the effect of subcutaneous injection of dopamine (1
mg/kg) on gastrointestinal tract motility by morphological
examination of antral, duodenal and proximal colonic walls.
Specimens of antrum, duodenum and proximal colon were taken from group 4 (control) and group 5 (treated) at 15 min (maximal effective
time) post-injection of dopamine for light microscopic examination.
These results indicate that, subcutaneous dopamine injection at a
dose of 0.1 and 1 mg/kg caused a significant decrease in antral,
duodenal and proximal colonic motility. The effect of dopamine was
apparent by 5 min post-injection (gradual effect) and maximal effect
was obtained at 15 min. The effect tended to return to the baseline by
60 min post-injection of 0.1 mg/kg dopamine and 90 min postinjection
of 1 mg/kg dopamine.
Morphological examination of the antral, duodenal and proximal
colonic walls of 1 mg/kg dopamine treated rats revealed a widely
separated villi and a marked decrease in the thickness of the smooth
muscle layer. These findings support the hypothesis that dopamine is
capable of decreasing the contractile force of gastrointestinal tract.
On the basis of the above histological examination, the decrease in
thickness of smooth muscle layer and widening of the villi as
demonstrated in the present study implies an integral role in the
relaxant effect of dopamine in gastrointestinal motility.
Experiment III: In this experiment four groups of rats (Groups 6, 7,
8 and 9) were used to characterize the dopamine receptor subtype(s)
involved in the effect of dopamine on gastrointestinal tract motility of
adult male rats. Animals of group 6 were treated with a selective D1-
like receptors agonist SKF-38393. Rats of group 7 were treated with a
selective D2-like receptors agonist bromocriptine. whereas, animals of groups 8 and 9 were used to assess the effect of dopamine on
gastrointestinal tract motility after pre-treatment with a selective D1-
like receptors antagonist SCH-23390 (group 8) and a selective D2-like
receptors antagonist metoclopramide (group 9). The effect of
dopamine on the sympathetic nerve activity (Sciatic nerve) was also
studied in this experiment in an attempt to detect its mechanism(s) of
action.
Amplitude, frequency and motility indexes of antral, duodenal and
proximal colonic contractions were recorded before (control level)
and at 15 min post-injection of SKF-38393 and bromocriptine. Also,
these parameters were recorded before and at 15 min post-injection of
dopamine to rats pre-treated with SCH-23390 (Groups 8) and rats pretreated
with metoclopramide (Group 9).
The first part of this experiment was undertaken to compare the
mean amplitude, frequency and motility index of antral, duodenal and
proximal colonic motility responses of D1-like receptor activation and
D2-like receptor activation with that of dopamine at 15 min postinjection.
D1-like receptors activation non-significantly changed the
amplitude, frequency and motility index of antral, duodenal and
proximal colonic contractions. whereas, activation of D2-like
receptors significantly decreased these parameters. These results
suggest that under stimulated conditions dopamine acts through
activation of D2 receptors.The second part of this experiment was done to further confirm the
suggestion that dopamine acts via dopaminergic receptors. Dopamine
(1 mg/kg) was injected subcutaneously after pre-treatment with D1-
like receptor antagonist SCH-23390 and D2-like receptor antagonist
metoclopramide. Dopamine treatment after D1 receptor blockade did
not abolish the gastrointestinal relaxant effect of dopamine, whereas,
blockade of D2-like receptors completely abolished the dopaminerelaxant
effect. These results confirm the suggestion that
dopaminergic receptors (D2 receptors) are important for the inhibitory
effects of dopamine on gastrointestinal tract motility under stimulated
conditions.
Experiment IV: In this experiment two groups of rats (Groups 10
and 11) were used to evaluate antrral, duodenal and proximal colonic
motility responses to dopamine after α-adrenergic receptors blockade
with reserpine and β-adrenergic receptors blockade with propranolol.
Intraperitonealy injection of dopamine after pre-treatment with
reserpine caused a non-significant change in the mean levels of antral,
duodenal and proximal colonic motility. Injection of dopamine after
pre-treatment with propranolol resulted in a significant decrease in
mean levels of antral, duodenal and proximal colonic motility. These
results suggested that under stimulated conditions, D2-like receptors
play an important role in the relaxant effect of dopamine. Dopamine
via D2-like receptors has a relaxant effect on antral, duodenal and
proximal colonic motility. Stimulation of D2-like receptors causes indirect relaxant effect on gastrointestinal motility and this effect is α-
adrenergic dependent. We believe these observations suggest that
dopamine inhibits acetylcholine release under stimulated conditions
via presynaptic dopamine D2 receptors probably located on
postganglionic cholinergic neurons.
In the present study, antral, duodenal and proximal colonic
contractions were significantly increased after D1-like receptors
blockade, whereas, a non-significant change was observed after D1-
like receptor activation. These data demonstrated that under basal
conditions endogenous dopamine may alter the basal antral, duodenal
and proximal colonic contractions. Under normal physiological
conditions, gastrointestinal tract motility is under maximal tonic
dopaminergic inhibition through direct action on smooth muscle
dopamine D1 receptors in adult male rats.
In addition, the morphological examination of the antral, duodenal
and proximal colonic wall clearly established that gastrointestinal
local blood flow was under a vasodilator effect by dopamine. The data
presented herein highlight the mechanism by which dopamine
induced gastrointestinal vasodilation. SNA was significantly
decreased after dopamine and D2-like receptors activation, whereas a
non-significant change was observed after D1-like receptors
activation. These findings suggest that the additional vasodilator
action of dopamine thought to be via D1- and D2-like receptors. It has
been considered to be partly a direct action through postsynaptic D1-
like receptors activation and partly an indirect action through presynaptic D2-like receptors activation to inhibit norepinephrine
release.
This response is beyond the scope of this study, which focused
mainly on the role of dopamine in regulating gastrointestinal motility
and further studies are, however, necessary to elucidate the precise
role of dopamine in the blood flow.
Evaluation of the physiological action of dopamine on
gastrointestinal motility during fasting:
Experiment V: In this experiment the last three groups of rats were
used. One control group (Group 12) and two groups were used to
assess the effect of fasting (Group 13) and refeeding (Group 14) on
the responses of gastrointestinal tract motility to physiological action
of dopamine. Rats of group 13 fasted for 48 h, animals of group 14
refeeded for 24 h after a fasting period of 48 h. Amplitude, frequency
and motility indexes of antral, duodenal and proximal colonic
contraction were recorded in the control group and at 15 min postinjection
of dopamine (1 mg/kg) to fasted and refeeded rats.
Dopamine injection to fasted rats resulted in a significant decrease
in the mean levels of amplitude, frequency and motility index of
antral, duodenal and proximal colonic contractions. In the refeeded
rats dopamine significantly decreased the antral, duodenal and
proximal colonic motility. Moreover, antral, duodenal proximal
colonic relaxant effect of dopamine after fasting was lesser than after
refeeding.Results of this experiment revealed that fasting alter the effect of
dopamine on the gastrointestinal tract. Fasting partially reduced the
inhibitory effect of dopamine on the gastrointestinal motility.
Dopamine in the rat gastrointestinal tract seems to be of exogenous
origin and derived partially from dopamine containing foods.