Prevention of stress-induced gastric ulcers by dopamine agonists in the rat.

Abstract

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.

• Authors: D E Hernandez, J W Adcock, R C Orlando, K S Patrick, C B Nemeroff, A J Prange Jr
• Journal: Life sciences (Life Sci) Vol. 35 Issue 24 Pg. 2453-8 (Dec 10 1984) ISSN: 0024-3205 [Print] Netherlands
• PMID: 6513723 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Methylphenidate
• 4-hydroxymethylphenidate
• Domperidone
• Apomorphine
• Dextroamphetamine
• Dopamine

Topics

• Animals
• Apomorphine (therapeutic use)
• Dextroamphetamine (therapeutic use)
• Domperidone (pharmacology)
• Dopamine (physiology)
• Male
• Methylphenidate (analogs & derivatives, therapeutic use)
• Rats
• Rats, Inbred Strains
• Stomach Ulcer (etiology, physiopathology, prevention & control)
• Stress, Physiological