Neurochemical and toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridine to rat serotonin neurons in dissociated cell cultures

Journal Article · Tue May 01 04:00:00 EDT 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:6749047

Friedman, L K; Mytilineou, C ^[1]

---

1. Mount Sinai School of Medicine, New York, NY (USA)

Dissociated cell cultures from the pontine area of embryonic rat brain were used to study the sensitivity of serotonin (5-hydroxy-tryptamine (5-HT)) neurons to the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+). Treatment with MPTP (up to 100 microM) for 7 days did not cause degeneration of 5-HT neurons. A 50% inhibition of (3H)5-HT uptake caused by 100 microM MPTP was a direct effect on the 5-HT uptake carrier, reversed by washing for 7 days. Incubation of cultures with MPTP increased the intraneuronal levels of 5-HT and reduced the levels of 5-hydroxyindoleacetic acid, suggesting a reduction in 5-HT metabolism. MPTP reduced monoamine oxidase activity in the cultures, which probably led to the reduction in 5-HT metabolism. Exposure to MPP+ (0.5-10 microM) for 4 to 7 days decreased (3H)5-HT uptake and induced loss of neurons stained with antibodies against 5-HT. Comparison between 5-HT and dopamine (DA) neurons indicated a differential sensitivity to MPP+ toxicity with DA neurons being more susceptible. Analysis of the competition of MPP+ with the natural substrates for uptake sites of 5-HT and DA neurons demonstrated higher affinity of MPP+ for DA compared to 5-HT neurons. The lower affinity of MPP+ for 5-HT neurons could be responsible for the accumulation of lower MPP+ levels observed in pontine cultures and explain the resistance of 5-HT neurons to this toxin.

• OSTI ID: 6749047
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 253:2; ISSN 0022-3565; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550101 -- Behavioral Biology-- Tracer Techniques
550801 -- Morphology-- Tracer Techniques
551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINE OXIDASES
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CULTURES
CENTRAL NERVOUS SYSTEM
COMPARATIVE EVALUATIONS
DOPAMINE
DRUGS
EMBRYOS
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
MAMMALS
MEMBRANE TRANSPORT
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHENOLS
POLYPHENOLS
PTERIDINES
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SENSITIVITY
SEROTONIN
SOMATIC CELLS
SYMPATHOMIMETICS
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES