Sparteine monooxygenase in brain and liver: Identified by the dopamine uptake blocker ( sup 3 H)GBR-12935

Conference · Mon Feb 26 00:00:00 EST 1990 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5534100

Kalow, W; Tyndale, R F; Niznik, H B; Inaba, T ^[1]

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1. Univ. of Toronto, Ontario (Canada)

P450IID6 (human sparteine monooxygenase) metabolizes many drugs including neuroleptics, antidepressants, and beta-blockers. The P450IID6 exists in human, bovine, rat and canine brains, but in very low quantities causing methodological difficulties in its assessment. Work with ({sup 3}H)GBR-12935; 1-(2-(diphenylmethoxy) ethyl)-4-(3-phenyl propyl) piperazine has shown that it binds a neuronal/hepatic protein with high affinity ({approximately}7nM) and a rank order of inhibitory potency suggesting that the binding protein is cytochrome P450IID6. The binding was used to predict that d-amphetamine and methamphetamine would interact with P450IID6. Inhibition studies indicated that these compounds were competitive inhibitors of P450IID6. Haloperidol (HAL) and it's metabolite hydroxy-haloperidol (RHAL) are both competitive inhibitors of P450IID6 activity and were found to inhibit ({sup 3}H)GBR-12935 binding. K{sub i} values of twelve compounds (known to interact with the DA transporter or P450IID6) for ({sup 3}H)GRB-12935 binding and P450IID6 activity. The techniques are now available for measurements of cytochrome P450IID6 in healthy and diseased brain/liver tissue using radio-receptor binding assay techniques with ({sup 3}H)GBR-12935.

• OSTI ID: 5534100
• Report Number(s): CONF-9004153-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 4:3; Conference: 74. annual meeting of the Federation of American Societies for Experimental Biology, Washington, DC (United States), 1-5 Apr 1990; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BRAIN
ENZYME ACTIVITY
LIVER
BIOCHEMICAL REACTION KINETICS
DRUGS
ENZYME INHIBITORS
MAN
METABOLISM
MIXED-FUNCTION OXIDASES
RADIOASSAY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
BODY
CENTRAL NERVOUS SYSTEM
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PRIMATES
PROTEINS
REACTION KINETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques