Long-term retention of neurotoxic beta-carbolines in brain neuromelanin.
beta-Carbolines show structural resemblance to the neurotoxic N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and are metabolized to mitochondrial toxicants. Humans are continuously exposed to low levels of beta-carbolines through cooked food, coffee, alcoholic beverages and tobacco smoke. beta-Carbolines have previously been detected in higher levels in the pigmented substantia nigra than in the cortex of humans. The distribution of 3H-labelled harman and norharman in the brain of pigmented and albino mice and in frogs (a species having neuromelanin) was studied by tape-section and light-microscopic autoradiography. Furthermore, the binding of these beta-carbolines to dopamine-melanin and melanin granules from Sepia officinalis was examined. The results revealed a high affinity binding to melanin and a long-term retention (up to 30 days) in pigmented tissues, including neuromelanin-containing neurons of frogs after a single injection. The role of long-term exposure to food-related beta-carbolines and a retention of these compounds in pigment-containing neurons in the induction of idiopathic Parkinson's disease should be further considered.
Ostergren
A
A
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Annas
A
A
Skog
K
K
Lindquist
N G
NG
Brittebo
E B
EB
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002243:Carbolines / Q000032:analysis / Q000378:metabolism*; D005260:Female; D008543:Melanins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000502:physiology; D011896:Rana temporaria; D013995:Time
D002243:Carbolines; D008543:Melanins; C014121:neuromelanin