Mechanism of toxicity of MPTP: A cause of Parkinsonism in human beings

Thesis/Dissertation · Fri Jan 01 00:00:00 EST 1988

OSTI ID:5601152

Denton, T L

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was found in 1983 to cause a syndrome virtually identical to Parkinson's Disease in humans and other primates. The symptoms, as in idiopathic Parkinson's syndrome, are due to destruction of dopaminergic neurons in the pars compacta of the substantia nigra resulting in depletion of dopamine in the basal ganglia. The mechanism of toxicity was investigated with a dopamine containing cell line, PC12, a MPTP resistant variant (MPTP{sup r}), and synaptosomes from the striate cortex of mice, rats, guinea pigs and a monkey. The mechanism of acute effects was studied with membrane preparations from human and rat striate cortex. MPTP displaced ({sup 3}H)haloperidol from binding sites in human and rat striate cortex, but could not displace ({sup 3}H)flupenthixol, suggesting that MPTP is a D2 receptor ligand of equivalent potency in both species. MPTP was a competitive inhibitor of uptake of ({sup 3}H)dopamine in PC12 but did not accumulate in PC12 or in synaptosomes of rat, guinea pig, mouse or monkey striate cortex. 100 uM MPTP depleted catecholamine levels in PC12 cells by about 50%, without killing.

• Research Organization: California Univ., Los Angeles, CA (USA)
• OSTI ID: 5601152
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DOPAMINE
UPTAKE
NERVOUS SYSTEM DISEASES
PATHOGENESIS
PYRIDINES
TOXICITY
BRAIN
CELL MEMBRANES
GUINEA PIGS
MICE
MONKEYS
NERVE CELLS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DISEASES
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PRIMATES
RODENTS
SOMATIC CELLS
SYMPATHOMIMETICS
VERTEBRATES
550901* - Pathology- Tracer Techniques