The physiological and pathological reactions of the body to stress are very important clinically. Gastric and duodenal ulcers are quite common, and they are especially prone to occur and persist in stressful environments. Dopamine has been implicated in healing processes within the gastrointestinal tract; but the source of the dopamine was unknown.We determined that the pancreas synthesizes dopamine and releases it into the duodenum. Using immunohistochemistry, in situ hybridization, histochemistry, Western blotting, RT-PCR, and radioactive uptake studies, we also localized a source of dopamine in the gastric mucosa. Thus, dopamine may serve as a protective agent in the stomach as well as the intestinal lumen. The molecular target of gastrointestinal dopamine appears to be the D1b receptor. This suggests that a specific agonist to this receptor might prove useful in treating mucosal injuries. We started to use a model, where the dopamine D5 receptor was genetically lacking (D5 ko mice) to study the role of this receptor in the mucosal defense. We use ulcerogenic agents and study the development of gastric and duodenal ulcers in control and knockout mice( see bibliography and Tom R. Hollon, Martin J. Bek, Jean E. Lachowicz, Eva Mezey, Patricio Soares-da-Silva, Zhi Fang Liu, Alexander Grinberg, John Drago,, Marjorie A. Ariano, Heiner Westphal, Pedro A. Jose, and David R. Sibley: Mice Lacking D5 Dopamine Receptors Have Increased Sympathetic Tone and Are Hypertensive,submitted)

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002883-09
Application #
6533345
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2001
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Hunyady, B; Palkovits, M; Mezey, E (2000) Vesicular monoamine transporters in the rat stomach. J Physiol Paris 94:123-30
Mezey, E; Eisenhofer, G; Hansson, S et al. (1999) Non-neuronal dopamine in the gastrointestinal system. Clin Exp Pharmacol Physiol Suppl 26:S14-22