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Activation of Protein Kinase C Suppresses the γ‐Aminobutyric Acid B Receptor‐Mediated Inhibition of the Vesicular Release of Noradrenaline and Acetylcholine
Author(s) -
Taniyama Kohtaro,
Niwa Masami,
Kataoka Yasufumi,
Yamashita Kimihiro
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb11334.x
Subject(s) - stimulation , acetylcholine , ouabain , protein kinase c , medicine , sphingosine , endocrinology , neurotransmitter , receptor , chemistry , biology , biochemistry , kinase , sodium , organic chemistry
Modulation of the γ‐aminobutyric acid B (GABA B ) receptor‐mediated response by protein kinase C (PKC) was examined with regard to inhibition by stimulation of the GABA B receptor of stimulation‐evoked release of noradrenaline (NA) from slices of cerebellar cortex and of acetylcholine (ACh) from strips of ileum. 12‐ O ‐Tetradecanoylphorbol 13‐acetate (TPA) potentiated the high K + ‐evoked Ca 2+ ‐dependent release of NA and ACh, but not the ouabain‐evoked release, even in the presence of external Ca 2+ . The potentiating effect was antagonized by sphingosine, thereby suggesting that PKC participates in the exocytotic‐vesicular release of neurotransmitters, but does not do so in case of a nonvesicular release. GABA inhibited the high K + ‐evoked release of NA and ACh, but not the ouabain‐evoked Ca 2+ ‐independent release. The effect of GABA was mimicked by baclofen and was antagonized by phaclofen, thereby suggesting that stimulation of the GABA B receptor inhibits the vesicular but not the nonvesicular release of neurotransmitters. TPA suppressed the GABA B receptor‐mediated inhibition of high K + ‐evoked release of NA and ACh. The effect of TPA was antagonized by sphingosine. These results indicate that stimulation of the GABA B receptor inhibits the stimulation‐evoked Ca 2+ ‐dependent release of neurotransmitters and that activation of PKC suppresses the GABA B receptor‐mediated response.

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