Non-neuronal dopamine in the gastrointestinal system

1. Dopamine CDA) is a protective agent in the gastrointestinal (Gn tract in both rats and humans, Therefore, we have studied the site of DA production in rat and human GI tract using a variety of techniques, including immunoc ytochemistry (ICC), in situ hybridization histochemistry, reverse transcrip tion-polymerase chain reaction, HPLC, western blotting and immunoelectron m icroscopy, 2. We found very high concentrations of DA that persisted after chemical sy mpathectomy (CS) in the gastric juice, the stomach mucosa and in the pancre as. Both the stomach mucosa and the pancreas also had tyrosine hydroxylase (TN) activity, most of which remained after CS, Double-labelling ICC showed that acid-producing parietal cells and the exocrine pancreas must also be capable of producing DA, 3. We isolated rat stomach parietal cells by cell fractionation and found t hat both DA and TN activity are present in isolated (denervated) parietal c ells, These cells also have other features of aminergic cells: they are imm uno- (and mRNA) positive for the DA plasma membrane transporter and vesicul ar monoamine transporter(s), In both gastric and duodenal mucosa, we demons trated the presence of significant amounts of the D5 receptor that could se rve as a target for locally produced DA, 4. Because DA, its biosynthetic enzymes and ifs transporters are also found in parietal cells in the human stomach, a mucosal protective system involv ing DA could be important clinically.