A novel nonneuronal catecholaminergic system: exocrine pancreas synthesizes and releases dopamine.
Cells of the exocrine pancreas produce digestive enzymes potentially harmful to the intestinal mucosa. Dopamine has been reported to protect against mucosal injury. In looking for the source of dopamine in the small intestine, we found that the duodenal juice contains high levels of dopamine and that the pancreas itself has a high dopamine [and dihydroxyphenylalanine (dopa)] content that does not change significantly after chemical sympathectomy. Furthermore, we were able to demonstrate tyrosine hydroxylase (TH) activity in control pancreas as well as in pancreas from rats after chemical sympathectomy. Immunostaining and in situ hybridization histochemistry confirmed both the presence of TH, dopamine, and the dopamine transporter, and the mRNAs encoding TH and dopamine transporter, and the presence of both types of vesicular monoamine transporters in the exocrine cells of the pancreas. Since there are no catecholaminergic enteric ganglia in the pancreas, the above results indicate that pancreatic cells have all the characteristics of dopamine-producing cells. We suggest that the pancreas is an important source of nonneuronal dopamine in the body, and that this dopamine has a role in protecting the intestinal mucosa and suggests that dopamine D1b receptor agonists might be used to help mucosal healing in the gastrointestinal tract.
Mezey
E
E
Clinical Neuroscience Branch, National Institute of Neurological Diseases and Stroke, National Institute of Mental Health, Bethesda, MD 20892, USA.
Eisenhofer
G
G
Harta
G
G
Hansson
S
S
Gould
L
L
Hunyady
B
B
Hoffman
B J
BJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides; D016627:Oxidopamine; D010179:Pancreas / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000096:biosynthesis*; D013563:Sympathectomy, Chemical; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism*; D050492:Vesicular Biogenic Amine Transport Proteins
D000906:Antibodies; D017931:DNA Primers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D015347:RNA Probes; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D050492:Vesicular Biogenic Amine Transport Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D004295:Dihydroxyphenylalanine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine