Stimulation of dopamine synthesis and activation of tyrosine hydroxylase by phorbol diesters in rat striatum

Journal Article · Mon Mar 23 04:00:00 EST 1987 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(87)90242-6· OSTI ID:6934983

Onali, P; Olianas, M C

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), Journal Name: Life Sci.; (United States) Vol. 40:12; ISSN LIFSA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
AMINO ACIDS
AMPHETAMINES
ANALEPTICS
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
BRAIN
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARCINOGENS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DATA
DOPAMINE
DRUGS
ENZYME ACTIVITY
ENZYMES
ESTERS
EXPERIMENTAL DATA
HYDROXY ACIDS
HYDROXY COMPOUNDS
HYDROXYLASES
INFORMATION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHENOLS
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
POLYPHENOLS
RATS
RODENTS
SOMATIC CELLS
SYMPATHOMIMETICS
SYNERGISM
SYNTHESIS
TRACER TECHNIQUES
TRANSFERASES
TYROSINASE
TYROSINE
VERTEBRATES