Phorbol ester and calcium act synergistically to enhance neurotransmitter release by brain neurons in culture.
Preincubation of intact fetal brain neurons in culture with the phorbol ester TPA (12-O-tetradecanoyl phorbol-13-acetate) in the presence of calcium, resulted in the enhancement of the depolarization-induced, Ca2+-dependent neurotransmitter release by the cells. This effect was due to a marked decrease in the concentration of extracellular Ca2+ required to provoke the release. The concentration of Ca2+ needed to produce half-maximal release shifted from approx 0.1 mM in the absence of TPA to 0.018 mM in its presence. This activity of TPA was concentration-dependent (half-maximal effect at 4 nM TPA) and was also dependent on the presence of calcium during the preincubation period. The TPA-induced enhancement of the stimulated release was also observed when Ca2+ entry into the depolarized cells was partially inhibited by Co2+. The results suggest that TPA acts synergistically with Ca2+ to activate neuronal component(s) involved in Ca2+-dependent neurosecretion.
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D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D005333:Fetus; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D018377:Neurotransmitter Agents; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D004298:Dopamine