Phorbol ester and forskolin suppress the presynaptic inhibitory action of group-II metabotropic glutamate receptor at rat hippocampal mossy fibre synapse

Neuroscience. 1997 Sep;80(1):89-94. doi: 10.1016/s0306-4522(97)00098-5.


Selective activation of second messenger pathways were tested on presynaptic metabotropic glutamate receptor action at mossy fibre-CA3 synapses, using a rat hippocampal slice preparation. Application of the protein kinase C activator, phorbol 12,13-diacetate, or the adenylate cyclase activator, forskolin, markedly enhanced the mossy fibre field excitatory postsynaptic potentials, and suppressed the relative magnitude of the synaptic depression induced by (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine, an agonist at group-II metabotropic glutamate receptors. These effects were also observed in a low Ca2+ solution, suggesting that they were not due to saturation of transmitter release process. Inactive analogues of the respective activators (4alpha-phorbol 12,13-didecanoate and 1,9-dideoxyforskolin) neither enhanced the mossy fibre responses nor suppressed (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine-induced synaptic depression. These results suggest that the presynaptic inhibitory action of group-II metabotropic glutamate receptors at mossy fibre-CA3 synapses could be negatively regulated by protein kinase C- and cyclic AMP-dependent mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / pharmacology*
  • Colforsin / pharmacology*
  • Female
  • Hippocampus / drug effects*
  • Male
  • Phorbol Esters / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / drug effects*
  • Synapses / drug effects
  • Synaptic Transmission / drug effects*


  • Carcinogens
  • Phorbol Esters
  • Receptors, Metabotropic Glutamate
  • Colforsin