Activation of protein kinase C potentiates norepinephrine release from sinus node.
Localization of binding sites of [20-3H]phorbol-12,13-dibutyrate [( 3H]PDBu) and the involvement of Ca2+-phospholipid-dependent protein kinase (protein kinase C) in the release of norepinephrine (NE) from sympathetic nerve terminals in the guinea pig sinus node were investigated. There was a single class of specific [3H]PDBu binding sites in the heart. [3H]NE release from the sinus node preloaded with [3H]NE was evoked by electrical stimulation in superfusing medium containing Ca2+ or by the concomitant presence of Ca2+ ionophore and Ca2+, in Ca2+-free medium. 12-O-tetradecanoylphorbol-13-acetate (TPA) potentiated the evoked [3H]NE release. The effect of TPA was antagonized by both polymyxin B and H-7, inhibitors of protein kinase C. TPA increased the apparent affinities of electrical stimulation-evoked release for extracellular Ca2+. The possibility that protein kinase C plays a role in transmembrane signal transduction involved in the release of NE from peripheral adrenergic nerve terminals in the guinea pig sinus node warrants continued study.
Shuntoh
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Tanaka
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D000818:Animals; D001665:Binding Sites; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004789:Enzyme Activation; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism*; D012849:Sinoatrial Node / Q000378:metabolism*; D014316:Tritium
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010703:Phorbol Esters; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D014316:Tritium; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D009638:Norepinephrine