Inhibition of noradrenaline release by neuropeptide Y does not involve protein kinase C in mouse atria.
In this study, we investigated the possible involvement of protein kinase C in the inhibitory effect of neuropeptide Y (NPY) on the electrical stimulation-induced release of radioactivity from mouse atria incubated with [3H]-noradrenaline. The protein kinase C activators, phorbol dibutyrate (PDB, 0.001-1 mumol/l) and phorbol myristate acetate (PMA, 0.001-1 mumol/l), increased the release of noradrenaline in a concentration-dependent manner. Interestingly, the maximum effect on noradrenaline release was significantly greater for phorbol dibutyrate compared to phorbol myristate acetate. The enhancement produced by both phorbol esters was significantly reduced by the protein kinase C inhibitor, K-252a (1 mumol/l). In the presence of the concentration of either phorbol ester (PMA, 0.1 mumol/l, PDB 1 mumol/l), that was supramaximal for increasing the release of noradrenaline, NPY (0.3 mumol/l) significantly inhibited the release of noradrenaline. Moreover, in the presence of the protein kinase C inhibitors, K-252a (1 mumol/l) or polymyxin B (70 mumol/l), NPY (0.3 mumol/l) also significantly inhibited the release of noradrenaline. Therefore, it is concluded that protein kinase C is not involved in the prejunctional inhibitory effect of NPY on noradrenaline release in the mouse atria. Furthermore, since K-252a also inhibits cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase and myosin light chain kinase, it is likely that these kinases are also not involved in the inhibitory mechanism of NPY.
Foucart
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S
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Musgrave
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IF
Majewski
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D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D051379:Mice; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D002227:Carbazoles; D026121:Indole Alkaloids; D009478:Neuropeptide Y; D014316:Tritium; D015240:Phorbol 12,13-Dibutyrate; C049985:staurosporine aglycone; D011493:Protein Kinase C; D011112:Polymyxin B; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine