Catecholamine uptake sites: characterization, localization, and a role in the production of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1985

OSTI ID:6788330

Javitch, J A

Dopamine and norepinephrine are inactivated by specific high affinity transport systems which mediate the recapture of the amines into presynaptic nerve terminals. (/sup 3/H)Maxindol labels neuronal dopamine uptake sites in corpus striatum membranes and neuronal norepinephrine uptake sites in cerebral cortex and submaxillary/sublingual gland membranes. The potencies of various inhibitors of biogenic amine uptake in reducing (/sup 3/H)mazindol binding in striatal membranes correlate with their potencies for inhibition of neurona (/sup 3/H)dopamine accumulation, whereas their potencies in reducing (/sup 3/H)mazindol binding to cortical and salivary gland membranes correlate with their potencies for inhibition of neuronal (/sup 3/H)norepinephrine accumulation. The association of (/sup 3/H)mazindol binding sites with neuronal dopamine uptake sites in the corpus striatum is further supported by the reduction of (/sup 3/H)mazindol binding sites in striatal membranes following destruction of dopaminergic neurons by 6-hydroxydopamine. Similarly, destruction of noradrenergic neurons by N-(2-chloro-ethyl)-N-ethyl-2-bromobenzylamine(DSP-4) decreases (/sup 3/H)mazindol binding to cortical membranes. Dopamine and norepinephrine uptake sites in rat brain have been differentially visualized using (/sup 3/H)mazindol autoradiography. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathologic and clinical abnormalities in humans and animals that closely resemble idiopathic Parkinson disease. (/sup 3/H)MPTP binds with high affinity to brain membranes. The chemical specificity of the binding sites corresponds to structure-activity requirements for neurotoxicity.

• Research Organization: Johns Hopkins Univ., Baltimore, MD (USA)
• OSTI ID: 6788330
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
AZINES
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CATECHOLAMINES
CENTRAL NERVOUS SYSTEM
DISEASES
DOPAMINE
DRUGS
GLANDS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
MEMBRANE TRANSPORT
NERVES
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NEUROREGULATORS
NORADRENALINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PHENOLS
POLYPHENOLS
PYRIDINES
SALIVARY GLANDS
STEROID HORMONES
SYMPATHOMIMETICS
TRITIUM COMPOUNDS
UPTAKE