Activation of protein kinase C suppresses the gamma-aminobutyric acidB receptor-mediated inhibition of the vesicular release of noradrenaline and acetylcholine.
Modulation of the gamma-aminobutyric acidB (GABAB) receptor-mediated response by protein kinase C (PKC) was examined with regard to inhibition by stimulation of the GABAB 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 Ca2+-dependent release of NA and ACh, but not the ouabain-evoked release, even in the presence of external Ca2+. 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 GABAB receptor inhibits the vesicular but not the nonvesicular release of neurotransmitters. TPA suppressed the GABAB 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 GABAB receptor inhibits the stimulation-evoked Ca(2+)-dependent release of neurotransmitters and that activation of PKC suppresses the GABAB receptor-mediated response.
Taniyama
K
K
2nd Department of Pharmacology, Nagasaki University School of Medicine, Japan.
Niwa
M
M
Kataoka
Y
Y
Yamashita
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011963:Receptors, GABA-A; D010042:Ouabain; D011493:Protein Kinase C; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D009638:Norepinephrine