Reduced adenosine release from the aged mammalian heart.

Adenosine (ADO) released in the heart results in enhanced coronary blood flow and reduced catecholamine release and myocardial responsiveness to adrenergic stimulation (anti-adrenergic action). ADO release from the adrenergic-stimulated aged heart is less than that from the young adult heart. Because adrenergic signaling in the aged heart is impaired, this study was conducted to determine if reduced ADO release from the aged heart results from this reduced adrenergic responsiveness.

Crosstalk between adenosine A1 and β1-adrenergic receptors regulates translocation of PKCε in isolated rat cardiomyocytes.

Adenosine A(1) receptor (A(1)R)-induced translocation of PKCε to transverse (t) tubular membranes in isolated rat cardiomyocytes is associated with a reduction in β(1)-adrenergic-stimulated contractile function. The PKCε-mediated activation of protein kinase D (PKD) by endothelin-1 is inhibited by β(1)-adrenergic stimulated protein kinase A (PKA) suggesting a similar mechanism of A(1)R signal transduction modulation by adrenergic agonists may exist in the heart. We have investigated the influence of β(1)-adrenergic stimulation on PKCε translocation elicited by A(1)R.

Myocardial adenosine A(1)-receptor-mediated adenoprotection involves phospholipase C, PKC-epsilon, and p38 MAPK, but not HSP27.

Adenosine via an adenosine A(1) receptor (A(1)R) is a negative feedback inhibitor of adrenergic stimulation in the heart, protecting it from toxic effects of overstimulation. Stimulation of the A(1)R results in the activation of G(i) protein, release of free Gbetagamma-subunits, and activation/translocation of PKC-epsilon to the receptor for activated C kinase 2 protein at the Z-line of the cardiomyocyte sarcomere. Using an anti-Gbetagamma peptide, we investigated the role of these subunits in the A(1)R stimulation of phospholipase C (PLC), with the premise that the resulting diacylglycerol provides for the activation of PKC-epsilon.

Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-epsilon to RACK2 in adult rat and mouse.

Adenosine protects the heart from adrenergic overstimulation. This adenoprotection includes the direct anti-adrenergic action via adenosine A(1) receptors (A(1)R) on the adrenergic signaling pathway. An indirect A(1)R-induced attenuation of adrenergic responsiveness involves the translocation of PKC-epsilon to t-tubules and Z-line of cardiomyocytes.

Adenosine A2A and beta-adrenergic calcium transient and contractile responses in rat ventricular myocytes.

The adenosine A2A receptor (A2AR) enhances cardiac contractility, and the adenosine A1R receptor (A1R) is antiadrenergic by reducing the adrenergic beta1 receptor (beta1R)-elicited increase in contractility. In this study we compared the A2AR-, A1R-, and beta1R-elicited actions on isolated rat ventricular myocytes in terms of Ca transient and contractile responses involving PKA and PKC. Stimulation of A2AR with 2 microM (approximately EC50) CGS-21680 (CGS) produced a 17-28% increase in the Ca transient ratio (CTR) and maximum velocities (Vmax) of transient ratio increase (+MVT) and recovery (-MVT) but no change in the time-to-50% recovery (TTR).

Adenosine A1 and A2A receptor regulation of protein phosphatase 2A in the murine heart.

Adenosine plays a role in regulating the contractile function of the heart. This includes a positive ionotropic action via the adenosine A(2A) receptor (A(2A)R) and an inhibition of beta(1)-adrenergic receptor-induced ionotropy (antiadrenergic action) via the adenosine A(1) receptor (A(1)R). Phosphatase activity has also been shown to influence contractile function by affecting the level of protein phosphorylation.

Adenosine A1 and A2A receptor effects on G-protein cycling in beta-adrenergic stimulated ventricular membranes.

In the heart beta1-adrenergic (beta1R) and adenosine A1 (A1R) and A2A (A2AR) receptors modulate contractile and metabolic function. The interaction between these receptors was investigated at the level of G-protein cycling by determining the effect of receptor agonists on the binding of GTP to G-proteins and displacement of G alpha-subunit-bound GDP by GTP. Crude membranes from rat heart or brain were stimulated by agonists for beta1R (isoproterenol; ISO), A1R (chlorocyclopentyladenosine, CCPA) and A2AR (CGS-21680; CGS).

Endogenous adenosine inhibits CNS terminal Ca(2+) currents and exocytosis.

Bursts of action potentials (APs) are crucial for the release of neurotransmitters from dense core granules. This has been most definitively shown for neuropeptide release in the hypothalamic neurohypophysial system (HNS). Why such bursts are necessary, however, is not well understood.

Contractile effects of adenosine A1 and A2A receptors in isolated murine hearts.

The adenosine A1 receptor (A1R) inhibits beta-adrenergic-induced contractile effects (antiadrenergic action), and the adenosine A2A receptor (A2AR) both opposes the A1R action and enhances contractility in the heart. This study investigated the A1R and A2AR function in beta-adrenergic-stimulated, isolated wild-type and A2AR knockout murine hearts. Constant flow and pressure perfused preparations were employed, and the maximal rate of left ventricular pressure (LVP) development (+dp/dt(max)) was used as an index of cardiac function.

Inhibition of phosphatase activity enhances preconditioning and limits cell death in the ischemic/reperfused aged rat heart.

Brief, nonlethal episodes of ischemia in the mammalian heart provide cardioprotection against the detrimental effects of a longer duration ischemia. The manifestation of this preconditioning (PC) phenomenon is initiated by the enhanced phosphorylation state of signal transduction proteins. We reported previously that PC is decreased in the aged rat myocardium.

Receptors subtypes involved in adenosine-mediated modulation of norepinephrine release from cardiac nerve terminals.

The objective of this study was to determine which adenosine receptor subtypes were involved in the modulation of norepinephrine release from cardiac nerve terminals. In addition, the persistence of adenosine-mediated effects was evaluated. Rat hearts attached to the stellate ganglion were isolated and perfused.

Protein kinase Cepsilon and the antiadrenergic action of adenosine in rat ventricular myocytes.

Adenosine-induced antiadrenergic effects in the heart are mediated by adenosine A(1) receptors (A(1)R). The role of PKCepsilon in the antiadrenergic action of adenosine was explored with adult rat ventricular myocytes in which PKCepsilon was overexpressed. Myocytes were transfected with a pEGFP-N1 vector in the presence or absence of a PKCepsilon construct and compared with normal myocytes.

Beta-adrenergic and antiadrenergic modulation of cardiac adenylyl cyclase is influenced by phosphorylation.

Adenosine protects the myocardium of the heart by exerting an antiadrenergic action via the adenosine A1 receptor (A1R). Because beta 1-adrenergic receptor (beta 1R) stimulation elicits myocardial protein phosphorylation, the present study investigated whether protein kinase A (PKA) catalyzed rat heart ventricular membrane phosphorylation affects the beta 1R adrenergic and A1R adenosinergic actions on adenylyl cyclase activity. Membranes were either phosphorylated with PKA in the absence/presence of a protein kinase inhibitor (PKI) or dephosphorylated with alkaline phosphatase (AP) and assayed for adenylyl cyclase activity (AC) in the presence of the beta 1R agonist isoproterenol (ISO) and/or the A1R agonist 2-chloro-N6-cyclopentyladenosine (CCPA).

Anoxia-induced changes in purine nucleoside metabolism of in vitro aged human fibroblasts.

Inosine deriving from the metabolism of adenosine or inosine monophosphate (IMP) in the fibroblast provides the substrate for xanthine oxidase and is, therefore, an important source of toxic oxygen free radicals. With well-oxygenated medium, adenosine release appears to be greater for aged than young fibroblasts. In that the adenosine release by young cells is enhanced by reduced oxygenation, the effect anoxic stress on the release of the purine nucleosides adenosine and inosine by low-passage (PDL 23-26; young) vs.