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A Decrease in [Ca 2+ ] c but not in cAMP Mediates L‐AP4 Inhibition of Glutamate Release: PKC‐mediated Suppression of this Inhibitory Pathway
Author(s) -
Herrero Inmaculada,
Vázquez Elena,
MirasPortugal M. Teresa,
SánchezPrieto José
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01255.x
Subject(s) - forskolin , glutamate receptor , inhibitory postsynaptic potential , protein kinase c , staurosporine , pertussis toxin , protein kinase a , stimulation , biology , arachidonic acid , biophysics , signal transduction , chemistry , microbiology and biotechnology , endocrinology , biochemistry , g protein , kinase , receptor , enzyme
We investigated the mechanism of the inhibition of glutamate release by L‐2‐amino‐4‐phosphonobutyrate (L‐AP4) in cerebrocortical nerve terminals from young rats (3 weeks of age). The Ca 2+ ‐dependent release of glutamate was reduced by L‐AP4 in a concentration‐dependent manner. This inhibitory effect was prevented by pertussis toxin, insensitive to staurosporine and associated with a reduction both in the depolarization‐evoked increase in the cytoplasmic free Ca 2+ concentration ([Ca 2+ ] c ) and in forskolin‐stimulated cAMP formation. However, the reduction in [Ca 2+ ] c but not in cAMP seemed to be responsible for the decrease in release, since inhibition by L‐AP4 can also be observed in the absence of detectable changes in CAMP. The inhibitory modulation by L‐AP4 was suppressed by the activation of protein kinase C with phorbol esters. The nerve terminals from young rats also exhibited a facilitatory pathway of glutamate release which was mediated by protein kinase C. Interestingly, stimulation of this pathway with the glutamate agonist (1 S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylate in the presence of arachidonic acid also abolished the inhibitory action of L‐AP4. The dominance of the facilitatory pathway in its interaction with the L‐AP4‐mediated inhibitory control may provide some clues to understand the presynaptic changes during synaptic plasticity.