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Central nervous system and gut interactions: Dopamine and experimental gastroduodenal lesions
Author(s) -
GLAVIN G. B.,
HALL A. M.
Publication year - 1994
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.1994.tb01299.x
Subject(s) - medicine , dopamine , central nervous system , gastroduodenal ulcer , gastroenterology , peptic ulcer
There is increasing evidence for brain regulation of gastroduodenal function and pathological responses. This laboratory has demonstrated a significant role for dopamine (DA) as a modulator of gastrointestinal function and disease. Using models of both acute (ethanol restraint stress; cysteamine) and chronic (iodoacetamide‐induced gastritis) gastroduodenal mucosal injury, as well as tests of gastric secretory function (conscious basal gastric acid secretion; pylorus ligation; ex vivo gastric chamber), we have shown that DA, particularly DA 1 /D 1 receptor agonists are powerful gastroprotective agents. This action is demonstrable upon peripheral administration as well as central (particularly intramesolimbic) administration. DA 1 /D 1 agonists such as SKF38393 and SKF75670C reduce experimental gastric mucosal injury and secretion while antagonists of these receptors, including SCH23390, worsen experimental gastroduodenal lesions and augment secretion. That there exists a significant central component to DA‐induced gastroprotection is demonstrated by data showing that rats assessed as anxiety prone, develop a greater degree of experimentally induced gastric damage, require greater amounts of DA agonists for 50% gastroprotection and respond to exogenous stress challenge with greater central DA turnover and loss, relative to rats assessed as low in anxiety. Very recently, we showed that dopamine D 4 receptor blockade by clozapine and activation of dopamine D 3 receptors by 7‐hydroxy‐ N , N ‐di‐ n ‐propyl‐2‐aminotetralin (7‐OHDPAT) are also associated with antisecretory and gastroprotective effects. Taken together, these data suggest that: (i) DA is a significant component of endogenous gastroprotection; (ii) central DA, particularly mesolimbic DA, is an important determinant of peripheral gastroduodenal responses to exogenous chemical and stress challenges; and (iii) the hypothesis that several DA receptor subtypes modulate gastroduodenal function and pathology is increasingly plausible.