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Dopamine sulphate: an enigma resolved.

G Eisenhofer1, M W Coughtrie, D S Goldstein

  • 1Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1620, USA. ge@box-g.nih.gov

Clinical and Experimental Pharmacology & Physiology. Supplement
|July 1, 1999
PubMed
Summary
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Dopamine (DA) sulfate, abundant in plasma, originates mainly from the gastrointestinal tract, not sympathetic nerves. This highlights a gut-blood barrier detoxifying dietary amines and regulating endogenous dopamine.

Area of Science:

  • Biochemistry
  • Physiology
  • Pharmacology

Background:

  • Dopamine (DA) sulfate circulates at higher plasma concentrations than free DA, with its source and significance being unclear.
  • Understanding DA sulfate is crucial for comprehending dopamine metabolism and its physiological roles.

Purpose of the Study:

  • To investigate the origins and physiological significance of dopamine (DA) sulfate.
  • To elucidate the role of the gastrointestinal tract in DA sulfate production.
  • To explore the enzymatic 'gut-blood' barrier for detoxification and regulation of endogenous dopamine.

Main Methods:

  • Review of modern molecular and traditional clinical approaches.
  • Cloning and expression analysis of the human sulphotransferase isoenzyme SULT1A3.

Related Experiment Videos

  • Analysis of plasma DA sulfate levels in response to diet, sympathetic outflow changes, and infused DA.
  • Measurement of DA sulfate increments across various organs, particularly mesenteric organs.

    • Main Results:

    • The sulphotransferase SULT1A3, responsible for DA sulfate production, is highly expressed in the gastrointestinal tract but not the liver.
    • Dietary intake significantly impacts plasma DA sulfate, but a substantial endogenous source exists.
    • The gastrointestinal tract accounts for over 75% of DA sulfate production, indicating it as a major source.
    • A novel DA autocrine/paracrine system in the gut produces nearly 50% of the body's DA.

    Conclusions:

    • The gastrointestinal tract is the primary source of plasma DA sulfate, functioning as a 'gut-blood' barrier.
    • DA sulfate production reflects detoxification of dietary amines and regulation of endogenous gut-derived dopamine.
    • This highlights a novel 'third catecholamine system' involving gut-derived dopamine and its sulfate conjugate.