SUBSTANTIAL PRODUCTION OF DOPAMINE IN THE HUMAN GASTROINTESTINAL-TRACT

Considerable urinary excretion of dopamine metabolites indicates that large amounts of dopamine are produced in unknown locations of the bod y. This study assessed the contribution of mesenteric organs (gastroin testinal tract, spleen, and pancreas) to the total body production of dopamine in humans and examined the presence of the rate-limiting enzy me for dopamine synthesis, tyrosine hydroxylase, in gastrointestinal t issues. Blood sampled from an artery and portal and hepatic veins in e ight subjects and from arterial and renal venous sites in other subjec ts was analyzed for plasma concentrations of dopamine and its metaboli tes. The activity and distribution of tyrosine hydroxylase was also ex amined in tissue samples from the stomach and duodenum. Higher concent rations of dopamine and its metabolites in portal venous than arterial plasma indicated substantial production of dopamine by mesenteric org ans (12.0 nmol/min) amounting to 42-46% of the renal removal of circul ating dopamine metabolites. Tissue samples showed immunoreactive tyros ine hydroxylase in nonneuronal cell bodies and detectable levels of ty rosine hydroxylase enzyme activity. The results show that mesenteric o rgans produce close to half of the dopamine formed in the body, most o f which is unlikely to be derived from sympathetic nerves but may refl ect production in a novel nonneuronal dopaminergic system.