Summary
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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?
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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.
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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.
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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.
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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.
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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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DOI: https://doi.org/10.1007/BF00712916