Stimulation of dopamine synthesis and activation of tyrosine hydroxylase by phorbol diesters in rat striatum
In rat striatal synaptosomes, 4..beta..-phorbol 12-myristate 13-acetate (PMA) and 4 ..beta..-phorbol 12,13-dibutyrate (PDBu), two activators of Ca/sup 2 +/-phospholipid-dependent protein kinase (protein kinase C) increased dopamine (DA) synthesis measured by following the release of /sup 14/CO/sub 2/ from L-(1-/sup 14/C) tyrosine. Maximal stimulation (21-28% increase of basal rate) was produced by 0.5 ..mu..M PMA and 1 ..mu..M PDBu. 4 ..beta..-Phorbol and 4 ..beta..-phorbol 13-acetate, which are not activators of protein kinase C, were ineffective at 1 ..mu..M. PMA did not change the release of /sup 14/CO/sub 2/ from L-(1-/sup 14/C)DOPA. Addition of 1 mM EGTA to a Ca/sup 2 +/-free incubation medium failed to affect PMA stimulation. KCl (60 mM) enhanced DA synthesis by 25%. Exposure of synaptosomes to either PMA or PDBu prior to KCl addition resulted in a more than additive increase (80-100%) of DA synthesis. A similar synergistic effect was observed when the phorbol diesters were combined with either veratridine or d-amphetamine but not with forskolin and dibutyryl cyclic AMP. Pretreatment of striatal synaptosomes with phorbol diesters produced an activation of tyrosine hydroxylase (TH) associated with a 60% increase of the Vmax and a decrease of the Km for the pterine cofactor 6-methyl-5,6,7,8-tetrahydropterin. These results indicate that protein kinase C participates in the regulation of striatal TH in situ and that its activation may act synergistically with DA releasing agents in stimulating DA synthesis. 37 references, 3 figures, 3 tables.
- Research Organization:
- Univ. of Cagliari, Italy
- OSTI ID:
- 6934983
- Journal Information:
- Life Sci.; (United States), Vol. 40:12
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
DOPAMINE
BIOSYNTHESIS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
TYROSINASE
ENZYME ACTIVITY
AMPHETAMINES
BRAIN
CARBON 14 COMPOUNDS
EXPERIMENTAL DATA
NERVE CELLS
PHOSPHOTRANSFERASES
RATS
SYNERGISM
TRACER TECHNIQUES
TYROSINE
AMINES
AMINO ACIDS
ANALEPTICS
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARBOXYLIC ACIDS
CARCINOGENS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DATA
DRUGS
ENZYMES
ESTERS
HYDROXY ACIDS
HYDROXY COMPOUNDS
HYDROXYLASES
INFORMATION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHENOLS
PHOSPHORUS-GROUP TRANSFERASES
POLYPHENOLS
RODENTS
SOMATIC CELLS
SYMPATHOMIMETICS
SYNTHESIS
TRANSFERASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques