Polymyxin B, a selective inhibitor of protein kinase C, diminishes the release of noradrenaline and the enhancement of release caused by phorbol 12,13-butyrate.
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 mumol/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.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D011112:Polymyxin B / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011817:Rabbits
D010703:Phorbol Esters; D011113:Polymyxins; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D011112:Polymyxin B; D003000:Clonidine; D009638:Norepinephrine