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. 2023 Jun;396(6):1279-1290.
doi: 10.1007/s00210-023-02394-9. Epub 2023 Jan 31.

Investigation on the positive chronotropic action of 6-nitrodopamine in the rat isolated atria

José Britto-Júnior  1 , Antonio Tiago Lima  2 , Vivian Fuguhara  2 , Fabiola Z Monica  2 , Edson Antunes  2 , Gilberto De Nucci  2   3   4
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Investigation on the positive chronotropic action of 6-nitrodopamine in the rat isolated atria

José Britto-Júnior et al. Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun.

Abstract

6-Nitrodopamine (6-ND) is released from rat isolated atria being 100 times more potent than noradrenaline and adrenaline, and 10,000 times more potent than dopamine as a positive chronotropic agent. The present study aimed to investigate the interactions of 6-ND with the classical catecholamines, phosphodiesterase (PDE)-3 and PDE4, and the protein kinase A in rat isolated atria. Atrial incubation with 1 pM of dopamine, noradrenaline, or adrenaline had no effect on atrial frequency. Similar results were observed when the atria were incubated with 0.01 pM of 6-ND. However, co-incubation of 6-ND (0.01 pM) with dopamine, noradrenaline, or adrenaline (1 pM each) resulted in significant increases in atrial rate, which persisted over 30 min after washout of the agonists. The increased atrial frequency induced by co-incubation of 6-ND with the catecholamines was significantly reduced by the voltage-gated sodium channel blocker tetrodotoxin (1 µM, 30 min), indicating that the positive chronotropic effect of 6-ND is due in part to activation of nerve terminals. Pre-treatment of the animals with reserpine had no effect on the positive chronotropic effect induced by dopamine, noradrenaline, or adrenaline; however, reserpine markedly reduced the 6-ND (1 pM)-induced positive chronotropic effect. Incubation of the rat isolated atria with the protein kinase A inhibitor H-89 (1 µM, 30 min) abolished the increased atrial frequency induced by dopamine, noradrenaline, and adrenaline, but only attenuated the increases induced by 6-ND. 6-ND induces catecholamine release from adrenergic terminals and increases atrial frequency independently of PKA activation.

Keywords: Nitrocatecholamine; Phosphodiesterase PDE3/4 inhibitor; Protein kinase inhibitor; Reserpine treatment; Tetrodotoxin.

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References

    1. Amphoux A, Vialou V, Drescher E, Brüss M, Mannoury La Cour C, Rochat C, Millan MJ, Giros B, Bönisch H, Gautron S (2006) Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology 50(8):941–952. https://doi.org/10.1016/j.neuropharm.2006.01.005 - DOI - PubMed
    1. Bacq A, Balasse L, Biala G, Guiard B, Gardier AM, Schinkel A, Louis F, Vialou V, Martres MP, Chevarin C, Hamon M, Giros B, Gautron S (2012) Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response. Mol Psychiatry 17(9):926–939. https://doi.org/10.1038/mp.2011.87 - DOI - PubMed
    1. Bien HJ (1953) Zur pharmakologie des reserpin eines neuen Alkaloids aus Rauwolfia serpentina Benth [Pharmacology of reserpin, a new alkaloid from Rauwolfia serpentina Benth]. Experientia 15;9(3):107–110. Undetermined Language. https://doi.org/10.1007/BF02178342
    1. Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58(3):488–520. https://doi.org/10.1124/pr.58.3.5 - DOI - PubMed
    1. Brasch H (1993) Field stimulation-induced noradrenaline release from guinea-pig atria is modulated by pre-junctional a2-adrenoceptors and protein kinase C. Basic Res Cardiol 88:545–556 - DOI - PubMed

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