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Polymyxin B, a selective inhibitor of protein kinase C, diminishes the release of noradrenaline and the enhancement of release caused by phorbol 12,13-dibutyrate

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Summary

Slices of the rabbit hippocampus were labelled with 3H-noradrenaline, superfused continuously with a modified Krebs-Henseleit medium containing the uptake inhibitor cocaine and stimulated electrically (2 ms, 3 Hz, 24 mA, 5 V/cm). Phorbol 12,13-dibutyrate (PDB), a potent activator of protein kinase C (PKC), strongly enhanced the electrically-evoked overflow of tritium. In contrast, polymyxin B, a relatively selective inhibitor of PKC, diminished the evoked tritium overflow in a time-and concentration-dependent manner. The enhancement of the evoked overflow of tritium caused by PDB was strongly reduced in the presence of polymyxin B (100 μmol/l). These results suggest 1. that PKC may be involved in the physiological mechanism of action-potential-induced noradrenaline release from noradrenergic nerve terminals and 2. that the PDB-induced enhancement of noradrenaline release may be due to a direct activation of PKC.

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Abbreviations

PKC:

protein kinase C

PDB:

phorbol 12,13-dibutyrate

TPA:

12-O-tetradecanoyl 13-acetate

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Allgaier, C., Hertting, G. Polymyxin B, a selective inhibitor of protein kinase C, diminishes the release of noradrenaline and the enhancement of release caused by phorbol 12,13-dibutyrate. Naunyn-Schmiedeberg's Arch. Pharmacol. 334, 218–221 (1986). https://doi.org/10.1007/BF00505825

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  • DOI: https://doi.org/10.1007/BF00505825

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