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Participation of protein kinase C and regulatory G proteins in modulation of the evoked noradrenaline release in brain

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Summary

  1. 1.

    In the present paper two questions are discussed: (A) Does protein kinase C (PKC) participate in the modulation of evoked noradrenaline release in brain tissue? and (B) Is there any link between presynapticα 2-adrenoceptors and regulatory G proteins?

  2. 2.

    Slices of the middle part of the rabbit hippocampus, labeled with3H-noradrenaline, were superfused with medium containing the reuptake inhibitor cocaine. During superfusion the tissue was stimulated twice electrically for 2 min each.

  3. 3.

    The PKC activators 4β-phorbol 12,13-dibutyrate (4β-PDB) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) increased the stimulation-evoked transmitter release in a concentration-dependent manner. 4α-PDB and 4-O-methyl-TPA, which do not activate PKC, were without effect on transmitter release. Polymyxin B, an inhibitor of PKC, diminished the stimulus-evoked overflow and counteracted the effects of the phorbol esters. The increases in release caused by phorbol esters and theα 2-adrenoceptor antagonist yohimbine were additive.

  4. 4.

    Treatment of hippocampal tissue with islet-activating protein (IAP) orN-ethylmaleimide (NEM), both known to inactivate the regulatory G proteins Gi and Go by chemical modification, led to a marked increase in evoked noradrenaline release. In addition, the effects of both theα 2-adrenoceptor agonist clonidine and theα 2-adrenoceptor antagonist yohimbine were inhibited.

  5. 5.

    The facilitatory effects of IAP and NEM on transmitter release were not additive. In synaptosomes prepared from rabbit hippocampus two polypeptides with molecular weights corresponding to those ofα i andα o were32P-ADP-ribosylated with IAP. Pretreatment of synaptosomes with NEM reduced the subsequent ADP ribosylation by IAP concentration dependently.

  6. 6.

    The above results suggest that PKC is involved in the modulation of noradrenaline release in the rabbit hippocampus. The presynapticα 2-autoreceptors modulate transmitter release by a mechanism which is not directly affected by PKC. Theα 2-autoreceptor-mediated signals seem to be transduced across the plasma membrane via regulatory G proteins.

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Hertting, G., Allgaier, C. Participation of protein kinase C and regulatory G proteins in modulation of the evoked noradrenaline release in brain. Cell Mol Neurobiol 8, 105–114 (1988). https://doi.org/10.1007/BF00712916

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