Central antisecretory and peripheral gastroprotective effects of GBR 12909, a selective dopamine uptake inhibitor.

A variety of dopaminergic compounds influence gastric secretion and response to injury. In particular, agonists of the D1 receptor are gastroprotective when given either centrally of peripherally. In the present studies, we show that an indirect dopamine (DA) promoter, GBR 12909, a selective DA uptake inhibitor given ip but not icv, protects against restraint-cold stress-induced gastric mucosal injury. This protection likely occurred through preservation of gastric adherent mucus, since all doses of GBR 12909 resulted in gastric mucus levels at or near control (non-stressed) values. When given, ip, GBR 12909 did not influence basal gastric acid secretion in conscious rats, however, when given icv, GBR 12909 inhibited gastric acid secretion with an ED50 of about 0.5 microgram (1.13 umoles). We conclude that both central and peripheral DA contributes to gastrointestinal integrity through reduction of aggressive elements in the gut as well as by enhancing gastric mucosal defence.