The influence of activation or inhibition of protein kinase C on the release of radioactivity from rat isolated atria labelled with [3H]-noradrenaline.
1. The release of radioactivity from rat isolated atria preloaded with [3H]-noradrenaline ([3H]-NA) evoked by electrical field stimulation (2 Hz, 1 ms, 60 s) of intraneuronal sympathetic nerves, high potassium (64.7 mM) or tyramine (0.3 micron) was used as an index of noradrenaline release. 2. Activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) produced a concentration-dependent enhancement of field stimulation-induced outflow of radioactivity, whereas polymyxin B, an inhibitor of protein kinase C, reduced [3H]-NA release evoked by field stimulation. The enhancement observed in the presence of PMA was attenuated by polymyxin B (10 and 70 microns). 3. Release of noradrenaline evoked by membrane depolarization in a high potassium medium was similarly affected by PMA and polymyxin B. 4. In contrast, the release of noradrenaline evoked by the indirectly acting sympathomimetic amine, tyramine, was not altered by PMA. Polymyxin B in a concentration of 70 microns, but not 10 microns caused a slight reduction in tyramine-induced outflow of radioactivity. 5. The spontaneous outflow of radioactive compounds was not affected by either PMA or polymyxin B in the bathing medium. 6. The findings suggest that protein kinase C may play a role in the exocytotic release of noradrenaline but not in the displacement of noradrenaline by indirectly acting sympathomimetic amines.
Ishac
E J
EJ
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
De Luca
A
A
D000818:Animals; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D013779:Tetrodotoxin; D011493:Protein Kinase C; D011112:Polymyxin B; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D009638:Norepinephrine; D014439:Tyramine