Prevention of stress-induced gastric ulcers by dopamine agonists in the rat.
Dopamine (DA) and DA agonists have been shown to exert a protective role against the formation of duodenal ulcers. The effect of stimulation of DA receptors on the development of stress-induced gastric ulcers is currently unknown. Accordingly, we evaluated the effect of several DA agonists on the development of gastric ulcers induced by 3 h of cold + restraint stress (CRS) in rats. Apomorphine, d-amphetamine, methylphenidate, and threo-dl-p-hydroxymethylphenidate (an hydroxylated analog of methylphenidate), significantly reduced both the incidence and severity of CRS-induced gastric ulcers. The gastric cytoprotection afforded by these agents was dose-related, and completely antagonized by pretreatment with the peripherally acting DA antagonist domperidone. Because domperidone blocks peripheral, but not central, DA receptors, and since the entry of threo-dl-p-hydroxymethylphenidate across the blood-brain barrier into the brain is restricted to a great extent, we conclude that stimulation of peripheral DA receptors is primarily involved in the gastric cytoprotection induced by dopamimetics.
D000818:Animals; D001058:Apomorphine / Q000627:therapeutic use*; D003913:Dextroamphetamine / Q000627:therapeutic use*; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D008297:Male; D008774:Methylphenidate / Q000031:analogs & derivatives / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013312:Stress, Physiological
D008774:Methylphenidate; C033296:4-hydroxymethylphenidate; D004294:Domperidone; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine