Phorbol esters potentiate rapid dopamine release from median eminence and striatal synaptosomes

Journal Article · Wed Jun 01 04:00:00 EDT 1988 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-122-6-2699· OSTI ID:7138483

Shu, C; Selmanoff, M

In the present study, we investigated the ability of phorbol esters to potentiate Ca2+-dependent depolarization-induced release of tritium-labeled dopamine ((3H)DA) from median eminence and striatal synaptosomes. Phorbol esters potentiated (3H)DA release in a concentration-dependent manner in both kinds of dopaminergic nerve terminals and with a potency series similar to that reported for stimulation of protein kinase-C (PKC) activity in other cell systems. Evoked (3H)DA release was increased by 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-7) M) after 1, 3, 5, and 10 sec of depolarization. The effect of TPA was suppressed by sphingosine, a PKC inhibitor. TPA enhanced (3H)DA release evoked by high K+, veratridine or the Ca2+ ionophore A23187. Phorbol ester potentiation was found to be depolarization dependent, as it was present from 30-75 mM, but not at 5-20 mM external K+. Potentiation was seen at all external Ca2+ concentrations studied between 0.01-3 mM. However, in the absence of external free Ca2+ (i.e. with 0.1 mM EGTA), the phorbol effect was not present. These data indicate that an increase in intrasynaptosomal Ca2+ concentration is necessary for the enhancement of (3H)DA release by phorbol esters to occur. The combination of TPA and the Ca2+ ionophore A23187 does not show the marked synergism observed in some other systems, that is maximal release was not reinstated. This suggests that in dopaminergic nerve terminals, activation of PKC has a modulatory, rather than a mediating, effect on release. Recently, we have shown that hyperprolactinemia stimulated (3H)DA release from median eminence synaptosomes by an external Ca2+-independent mechanism which might involve the PKC pathway. However, in the present work we found that the TPA and PRL effects on evoked (3H)DA release were additive, suggesting that two independent mechanisms are involved.

• Research Organization: Univ. of Maryland School of Medicine, Baltimore (USA)
• OSTI ID: 7138483
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 122:6; ISSN ENDOA
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METALS
ALKALINE EARTH METAL COMPOUNDS
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
CALCIUM COMPOUNDS
CARCINOGENS
CARDIOTONICS
CARDIOVASCULAR AGENTS
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELEMENTS
ENZYME INHIBITORS
ESTERS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
METALS
NERVE CELLS
NEUROREGULATORS
ORGANIC COMPOUNDS
PHENOLS
PHORBOL ESTERS
POLYPHENOLS
POTASSIUM
RATS
REACTION KINETICS
RODENTS
SECRETION
SOMATIC CELLS
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES