Phorbol ester and forskolin suppress the presynaptic inhibitory action of group-II metabotropic glutamate receptor at rat hippocampal mossy fibre synapse.
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.
Kamiya
H
H
Department of Physiology, Faculty of Medicine, Kanazawa University, Japan.
Yamamoto
C
C
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D002273:Carcinogens; D010703:Phorbol Esters; D018094:Receptors, Metabotropic Glutamate; D005576:Colforsin