Dopamine receptor sub-types in gastric and duodenal ulceration

Conflicting reports in the literature exist, regarding the role of dopamine in the genesis of gastric and duodenal ulceration, gastric cytoprotection, gastric acid secretion, gastro-intestinal motility and in the strengthening of gastric mucosal barrier. Dopamine and its agonists have been shown to exert a protective role against the formation of gastric and duodenal ulcers, whereas, dopamine antagonists are reported to produce pro-ulcerogenic effects. However, many reports conflict with this view as selective dopamine D2 receptor antagonists have been shown to be beneficial when used as an adjunct in peptic ulcer disease. After reviewing the available literature and taking into consideration our own findings it appears that dopamine D1 and D2 receptors have opposing effects on gastric and duodenal ulceration, gastrointestinal motility, gastric mucosal blood flow and gastric acid secretion. While dopamine D2-receptor antagonists like sulpiride and domperidone produce anti-ulcer effect, dopamine D1-receptor antagonists like SCH 23390, SCH 39166, pimozide, butaclamol and spiperone, which possess more dopamine D1-activity have been reported to produce ulcerogenic activity in various models of gastric and duodenal ulcers. The above observations pinpoint the functional importance of the dopamine receptor subtypes namely the D1 and D2-receptors, present both centrally and peripherally in modulating the normal gastro-intestinal functions. Existence of a functionally significant dopaminergic brain-gut axis has also been proposed.