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Substantial Production of Dopamine in the Human Gastrointestinal Tract

Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (G.E., D.H., B.H., E.M.), Bethesda, Maryland 20892-1424; and Departments of Physiology and Clinical Physiology, University of Göteborg (A.A., P.F., L.F., H.L.), Göteborg, Sweden

Address all correspondence and requests for reprints to: Graeme Eisenhofer, Building 10, Room 4D20, National Institutes of Health 10 Center Drive, Bethesda, Maryland 20892-1424. E-mail: ge{at}box-g.nih.gov

Considerable urinary excretion of dopamine metabolites indicates that large amounts of dopamine are produced in unknown locations of the body. This study assessed the contribution of mesenteric organs (gastrointestinal tract, spleen, and pancreas) to the total body production of dopamine in humans and examined the presence of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, in gastrointestinal tissues. Blood sampled from an artery and portal and hepatic veins in eight subjects and from arterial and renal venous sites in other subjects was analyzed for plasma concentrations of dopamine and its metabolites. The activity and distribution of tyrosine hydroxylase was also examined in tissue samples from the stomach and duodenum. Higher concentrations of dopamine and its metabolites in portal venous than arterial plasma indicated substantial production of dopamine by mesenteric organs (12.0 nmol/min) amounting to 42–46% of the renal removal of circulating dopamine metabolites. Tissue samples showed immunoreactive tyrosine hydroxylase in nonneuronal cell bodies and detectable levels of tyrosine hydroxylase enzyme activity. The results show that mesenteric organs produce close to half of the dopamine formed in the body, most of which is unlikely to be derived from sympathetic nerves but may reflect production in a novel nonneuronal dopaminergic system.

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