Dopamine is linked to gastrointestinal functions. However, its exact nature in stress-induced gastric pathology is still not clear. In the present study, an attempt has been made to identify the effects of
dopamine in stress-induced
gastric ulcers, and concurrent alterations in various
ulcer-influencing factors such as plasma
corticosterone levels, gastric mucosal
PGE(2) content and
proton pump activity. The
dopamine D(1) receptor agonist (
A 68930) and antagonist (
SCH 23390), and D(2) receptor agonist (
quinpirole) and antagonist (
sulpiride) were used to evaluate their effects on acute stress (single immobilization for 150 min) and chronic unpredictable stress (two different types of stressors for 7 days) induced
gastric ulcers in rats. Acute and chronic unpredictable stress significantly increased the
gastric ulcer severity, adrenal
hypertrophy and
corticosterone levels, while gastric mucosal
dopamine levels were decreased. Pretreatment of
sulpiride (60 mg/kg) significantly reverted the acute stress-induced alterations, while
A 68930 (0.25mg/kg) significantly restored the acute and chronic unpredictable stress-induced alterations. In contrast, administration of
SCH 23390 (0.1-0.5mg/kg) and
quinpirole (0.1-0.5mg/kg) failed to alter acute stress-induced alterations. Further,
A 68930 and
sulpiride showed different response on
proton pump inhibition under in-vitro condition.
A 68930 (10-50 microg/ml) inhibited the
gastric H(+) K(+)-ATPase activity comparable to positive control
omeprazole, while
sulpiride (10-50 microg/ml) had no effect.
A 68930 also normalized the decreased gastric
PGE2 content observed during chronic unpredictable stress. The histopathological evaluation of gastric mucosal tissue supported the observations regarding the gastroprotective effect of
sulpiride during acute stress and of
A 68930 during both acute and chronic unpredictable stress conditions. Our results provide important insights into the mechanism of
dopamine-regulated pathways, which cause an overall pathophysiology of gastric stress
ulcers and implicating the importance of D(1) agonist in
ulcer protection. Thus, current study highlights the need to evaluate anti-stress and
anti-ulcer agents in terms of their ability to modulate dopaminergic transmissions.