Dopamine and the Brain-Gut Axis

Abstract

Publisher Summary Some dopaminergic compounds are reported to be efficient in the treatment of duodenal ulcer disease in humans and prevent gastroduodenal mucosal damage in animal models of ulcer disease. These findings in humans and animals made it of interest to investigate the effects of dopamine and dopaminergic compounds on duodenal mucosal bicarbonate secretion. The secretion has been studied in anesthetized animals and in human volunteers. The results of these studies are summarized and some recent findings are reported in this chapter. Animal studies of effects of dopamine and dopaminergic compounds have to consider that well-documented sites of action are the central nervous system as well as some peripheral tissues, including the intestinal tract and the kidney. Dopamine may exert effects not only on dopamine receptors, but also on adrenoceptors. Dopamine D 1 -receptor stimulation by bromocriptine, in contrast, caused a decrease in secretion. Catecholamine O-methyl transferase (COMT) inhibitors decrease tissue degradation of catecholamines, including dopamine. Interestingly, the centrally acting D 1 /D 2 antagonist haloperidol does not decrease but stimulates the duodenal secretion. Studies of isolated duodenal enterocytes lend strong support to the suggestion that dopamine stimulates duodenal mucosal bicarbonate secretion by an action on the duodenal enterocytes and confirm that stimulation is D 1 -receptor-mediated. On the other hand peripheral COMT inhibition increases duodenal mucosal bicarbonate secretion in human volunteers as well as in animals. These results indicate that duodenal secretion is stimulated via peripheral dopamine D 1 receptors. The stimulation of the secretion by haloperidol may suggest the presence of central nervous as well as peripheral dopaminergic modulation of duodenal bicarbonate secretion and mucosal protection.