Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Mar;68:66-74.
doi: 10.1016/j.yjmcc.2013.12.030. Epub 2014 Jan 9.

Alpha-2 Adrenoceptors and Imidazoline Receptors in Cardiomyocytes Mediate Counterbalancing Effect of Agmatine on NO Synthesis and Intracellular Calcium Handling

Affiliations

Alpha-2 Adrenoceptors and Imidazoline Receptors in Cardiomyocytes Mediate Counterbalancing Effect of Agmatine on NO Synthesis and Intracellular Calcium Handling

Alexander V Maltsev et al. J Mol Cell Cardiol. .

Abstract

Evidence suggests that intracellular Ca(2+) levels and contractility of cardiomyocytes can be modulated by targeting receptors other than already identified adrenergic or non-adrenergic sarcolemmal receptors. This study uncovers the presence in myocardial cells of adrenergic α2 (α2-AR) and imidazoline I1 (I1R) receptors. In isolated left ventricular myocytes generating stationary spontaneous Ca(2+) transients in the absence of triggered action potentials, the prototypic agonist of both receptors agmatine can activate corresponding signaling cascades with opposing outcomes on nitric oxide (NO) synthesis and intracellular Ca(2+) handling. Specifically, activation of α2-AR signaling through PI3 kinase and Akt/protein kinase B stimulates NO production and abolishes Ca(2+) transients, while targeting of I1R signaling via phosphatidylcholine-specific phospholipase C (PC-PLC) and protein kinase C (PKC) suppresses NO synthesis and elevates averaged intracellular Ca(2+). We identified that endothelial NO synthase (eNOS) is a major effector for both signaling cascades. According to the established eNOS transitions between active (Akt-dependent) and inactive (PKC-dependent) conformations, we suggest that balance between α2-AR and I1R signaling pathways sets eNOS activity, which by defining operational states of myocellular sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) can adjust Ca(2+) re-uptake and thereby cardiac inotropy. These results indicate that the conventional catalog of cardiomyocyte sarcolemmal receptors should be expanded by the α2-AR and I1R populations, unveiling previously unrecognized targets for endogenous ligands as well as for existing and potential pharmacological agents in cardiovascular medicine.

Keywords: Cell signaling; Heart; Ryanodine receptor; SERCA; SR; eNOS.

Similar articles

See all similar articles

Cited by 1 article

Publication types

MeSH terms

LinkOut - more resources

Feedback