50 years of dopamine

Today’s issue of Nature contains a news feature about Arvid Carlsson, the Swedish pharmacologist who in the 1950s discovered dopamine and established that it acts as a neurochemical transmitter in the brain.

When Carlsson discovered dopamine in 1952, other pharmacologists were skeptical about his findings, and believed that dopamine was merely a metabolite of another transmitter. Dopamine is in fact an intermediate step in the biosynthesis of two other neurotransmitters. It is synthesized from the amino acid tyrosine, by the actions of the enzymes tyrosine hydroxylase, which removes a hydroxyl group (-OH) from tyrosine to produce levo-dopa, and DOPA decarboxylase, which removes a carboxy group (-COOH) from levo-dopa to produce dopamine. The actions of dopamine- β-hydroxylase then convert dopamine to adrenaline, which can is converted to noradrenaline by the enzyme phenylethanolamine-N-methyl transferase.

Another set of experiments by Carlsson, which were published in 1957, showed that dopamine was a transmitter in its own right. The experiments involved injecting rabbits with resperpine, a drug which prevents the uptake of various neurotransmitters, including dopamine and serotonin, by synaptic vesicles at nerve terminals. The effect of this drug is to deplete nerve terminals of these transmitters. Carlsson’s rabbits became catatonic as a result, but injection with the dopamine precursor levo-dopa restored their motor function, establishing that dopamine was in fact also a neurotransmitter. This also led to the discovery of dopamine’s involvement in Parkinson’s Disease, and the use of levo-dopa as a treatment for the condition. (The latter story was dramatized in the 1990 film Awakenings, directed by Penny Marshall). Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine for his work.

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