Synergism of myocardial β-adrenoceptor blockade and I1 -imidazoline receptor-driven signaling: Kinase-phosphatase switching

Biochemical and Biophysical Research Communications
Alexander V MaltsevYuri M Kokoz

Abstract

Recently identified imidazoline receptors of the first type (I1Rs) on the cardiomyocyte's sarcolemma open a new field in calcium signaling research. In particular, it is interesting to investigate their functional interaction with other well-known systems, such as β-adrenergic receptors. Here we investigated the effects of I1Rs activation on L-type voltage-gated Ca2+-currents under catecholaminergic stress induced by the application of β-agonist, isoproterenol. Pharmacological agonist of I1Rs (I1-agonist), rilmenidine, and the putative endogenous I1-ligand, agmatine, have been shown to effectively reduce Ca2+-currents potentiated by isoproterenol. Inhibitory analysis shows that the ability to suppress voltage-gated Ca2+-currents by rilmenidine and agmatine is fully preserved in the presence of the protein kinase A blocker (PKA), which indicates a PKA-independent mechanism of their action. The blockade of NO synthase isoforms with 7NI does not affect the intrinsic effects of agmatine and rilmenidine, which suggests NO-independent signaling pathways triggered by I1Rs. A nonspecific serine/threonine protein phosphatase (STPP) inhibitor, calyculin A, abrogates effects of rilmenidine or agmatine on the isoproterenol-induced Ca2+-cur...Continue Reading

Citations

Feb 25, 2021·Archives of Biochemistry and Biophysics·Alexander V MaltsevYury M Kokoz
Jun 4, 2019·Archives of Biochemistry and Biophysics·Alexander V MaltsevYury M Kokoz
Apr 27, 2021·Biochemical and Biophysical Research Communications·Alexander V Maltsev, Pavel M Balaban
Jun 3, 2021·International Journal of Molecular Sciences·Alexander V MaltsevPavel M Balaban

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