Evidence for the involvement of dopamine agonists and antagonists in duodenal ulcer disease.
In experimental duodenal ulceration, dopamine levels, turnover, and binding sites are influenced. Dopamine agonists and antagonists exert anti- and proulcerogenic effect, respectively, probably by influencing duodenal hyper- or hypomotility, rather than effecting gastric secretion. The duodenal ulcerogenic effect of the dopamine neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) given to rats in multiple daily doses (p.o. or s.c.) also induced in a dose-dependent manner duodenal ulcers. Duodenal ulcers were prevented by pretreatment with dopamine agonists (e.g. bromocriptine, lergotrile) or monoamine oxidase inhibitors (e.g. pargyline or 1-deprenyl). Our hypothesis suggests that duodenal ulcerogens may interfere with the action of dopamine resulting in loss of the inhibitory function of dopamine, and producing tissue damage from the accumulated auto-oxidation products of dopamine. Alternatively a motility disorder induced by cysteamine, propionitrile or MPTP may contribute to the pathogenesis probably by involving localized hyperacidity in the duodenal bulb because of decreased neutralization and impaired duodenal emptying of acid.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003543:Cysteamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004381:Duodenal Ulcer / Q000139:chemically induced*; D005750:Gastric Juice / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010189:Pancreatic Juice / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000502:physiology; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship
D009570:Nitriles; D011725:Pyridines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D003543:Cysteamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C005557:propionitrile; D008995:Monoamine Oxidase; D001058:Apomorphine; D004298:Dopamine; D009638:Norepinephrine