Gb. Glavin et Am. Hall, CENTRAL-NERVOUS-SYSTEM AND GUT INTERACTIONS - DOPAMINE AND EXPERIMENTAL GASTRODUODENAL LESIONS, Journal of gastroenterology and hepatology, 9, 1994, pp. 36-39
There is increasing evidence for brain regulation of gastroduodenal fu
nction 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 st
ress; cysteamine) and chronic (iodoacetamide-induced gastritis) gastro
duodenal mucosal injury, as well as tests of gastric secretory functio
n (conscious basal gastric acid secretion; pylorus ligation; ex: vivo
gastric chamber), we have shown that DA, particularly DA(1)/D-1 recept
or agonists are powerful gastroprotective agents. This action is demon
strable upon peripheral administration as well as central (particularl
y intramesolimbic) administration. DA(1)/D-1 agonists such as SKF38393
and SKF75670C reduce experimental gastric mucosal injury and secretio
n while antagonists of these receptors, including SCH23390, worsen exp
erimental gastroduodenal lesions and augment secretion. That there exi
sts a significant central component to DA-induced gastroprotection is
demonstrated by data showing that rats assessed as anxiety prone, deve
lop a greater degree of experimentally induced gastric damage, require
greater amounts of DA agonists for 50% gastroprotection and respond t
o exogenous stress challenge with greater central DA turnover and loss
, relative to rats assessed as low in anxiety. Very recently, we showe
d chat dopamine D-4 receptor blockade by clozapine and activation of d
opamine D-3 receptors by 7-hydroxy-N, N-di-n-propyl-2-aminotetralin (7
-OHDPAT) are also associated with antisecretory and gastroprotective e
ffects. Taken together, these data suggest that: (i) DA is a significa
nt component of endogenous gastroprotection; (ii) central DA, particul
arly mesolimbic DA, is an important determinant of peripheral gastrodu
odenal responses to exogenous chemical and stress challenges; and (iii
) the hypothesis that several DA receptor subtypes modulate gastroduod
enal function and pathology is increasingly plausible.