Sources and Physiological Significance of Plasma Dopamine Sulfate

Abstract

Dopamine in the circulation occurs mainly as dopamine sulfate, the sources and physiological significance of which have been obscure. In this study, plasma concentrations of dopamine sulfate were measured after a meal, after fasting for 4 days, and during i.v. L-DOPA, nitroprusside, or trimethaphan infusion in volunteers; after dopamine infusion in patients with L-aromatic-amino-acid decarboxylase deficiency; in arterial and portal venous plasma of gastrointestinal surgery patients; and in patients with sympathetic neurocirculatory failure. Meal ingestion increased plasma dopamine sulfate by more than 50-fold; however, prolonged fasting decreased plasma dopamine sulfate only slightly. L-DOPA infusion produced much larger increments in dopamine sulfate than in dopamine; the other drugs were without effect. Patients with L-aromatic amino acid decarboxylase deficiency had decreased dopamine sulfate levels, and patients with sympathetic neurocirculatory failure had normal levels. Decarboxylase-deficient patients undergoing dopamine infusion had a dopamine sulfate/dopamine ratio about 25 times less than that at baseline in volunteers. Surgery patients had large arterial-portal venous increments in plasma concentrations of dopamine sulfate, so that mesenteric dopamine sulfate production accounted for most of urinary dopamine sulfate excretion, a finding consistent with the localization of the dopamine sulfoconjugating enzyme to gastrointestinal tissues. The results indicate that plasma dopamine sulfate derives mainly from sulfoconjugation of dopamine synthesized from L-DOPA in the gastrointestinal tract. Both dietary and endogenous determinants affect plasma dopamine sulfate. The findings suggest an enzymatic gut-blood barrier for detoxifying exogenous dopamine and delimiting autocrine/paracrine effects of endogenous dopamine generated in a "third catecholamine system."

Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans

“…Other in vitro studies have demonstrated the formation of hydroxytyrosol as a result of 3,4-dihidroxyphenylacetaldehyde (DOPAL), a dopamine metabolite, reduction by the human liver alcohol dehydrogenase isoenzyme (Mardh & Vallee, 1986). Tyrosine derived from the breakdown of dietary protein could be a precursor of endogenous formation of dopamine in cells containing the tyrosine hydroxylase enzyme (Goldstein et al, 1999). Therefore, endogenous formation of hydroxytyrosol could be derived from the human metabolism of dietary tyrosine.…”

Cytosolic Sulfotransferase 1A3 Is Induced by Dopamine and Protects Neuronal Cells from Dopamine Toxicity

“…It is essential in the presystemic elimination of dietary dopamine and other catecholamines. Moreover, gut SULT1A3 appears to be responsible for the metabolism of circulating dopamine (23). The identification of SULT1A3 in the brain, including dopaminergic regions of the midbrain (24), raises the possibility that it has a role in eliminating dopamine in the brain as well.…”

Testing the Sulfotransferase Molecular Pore Hypothesis

“…This 13-member enzyme family transfers the sulfuryl moiety (-SO 3 ) from the universal donor 3Ј-phosphoadenosine 5Ј-phosphosulfate (PAPS; or activated sulfate) to the hydroxyls and primary amines of hundreds, perhaps thousands of acceptors (metabolites, drugs, and other xenobiotics) (1)(2)(3)(4). Sulfonation of small molecule activators of steroid (1-3), thyroid (5), and dopamine receptors (4) typically weakens their receptor binding affinities beyond the point of physiological relevance (6).…”