Amino Acids

, Volume 14, Issue 1–3, pp 175–179 | Cite as

Destruction of catecholamine-containing neurons by 6-hydroxydopa, an endogenous amine oxidase cofactor

  • R. M. Kostrzewa
  • R. Brus
Review Article

Summary

The amino acid, 6-hydroxydopa (6-OHDOPA), found at the active site of amine oxidases, exists as a keto-enol. Exogenously administered 6-OHDOPA is an excitotoxin likeβ-N-oxalylamino-L-alanine (BOAA) andβ-N-methylamino-L-alanine (BMAA), acting at the non-N-methyl-D-aspartate (non-NMDA)α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. BMAA and BOAA are causal factors of neurolathyrism in humans. Much exogenously administered 6-OHDOPA is biotransformed by aminoacid decarboxylase (AADC) to the highly potent and catecholamine (CA) selective neurotoxin, 6-hydroxydopamine (6-OHDA). 6-OHDOPA destroys locus coeruleus noradrenergic perikarya and produces associated denervation of brain by norepinephrine-(NE) containing fibers. Opiopeptides and opioids enhance neurotoxic effects of 6-OHDOPA on noradrenergic nerves, by a naloxone-reversible process. An understanding of mechanisms underlying neurotoxic effects of 6-OHDOPA can be helpful in defining actions of known and newfound amino acids and for investigating their potential neurotoxic properties.

Keywords

6-Hydroxydopa 6-Hydroxydopamine Noradrenergic neurons Neurotoxicity Excitatory amino acids 

Abbreviations

AADC

aminoacid decarboxylase

AMPA

α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid

BOAA

β-N-oxalylamino-Lalanine

CA

catecholamine

L-DOPA

L-dihydroxyphenylalanine

DA

dopamine

EAA

excitatory amino acid

6-OHDOPA

6-hydroxydopa

6-OHDA

6-hydroxydopamine

NE

norepinephrine

BMAA

β-N-methylamino-L-alanine

NMDA

N-methyl-D-aspartate

S.E.M.

standard error of the mean

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Copyright information

© Springer-Verlag 1998

Authors and Affiliations

  • R. M. Kostrzewa
    • 1
  • R. Brus
    • 2
  1. 1.Department of PharmacologyQuillen College of Medicine, East Tennessee State UniversityTennesseeU.S.A.
  2. 2.Department of PharmacologySilesian Academy of MedicineZabrzePoland

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