Accumulation and salvage of adenosine and inosine by isolated mature cardiac myocytes

Bowditch, Julia; Brown, Anne K.; Dow, Jocelyn W.

doi:10.1016/0167-4889(85)90082-5

Cited by 55 publications

(13 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…P 2 receptors are furthermore subdivided into P 2X (ligand-gated ion channels) and P 2Y receptors (G protein-coupled receptors). The mRNAs for all presently known P 2X receptors (P 2X1-7 ) and P 2Y receptors (P 2Y1, 2,4,6,11,12,13,14 ) were detected in the human heart (3,66). On protein level, P 2Y1,4,6,12 and P 2X1,2,3,4,6,7 have been detected in the human heart (3,66).…”

Section: Discussionmentioning

confidence: 99%

“…ATP can be degraded by soluble-or cell surface-located enzymes (ectonucleotidases and others) resident on endothelial cells but also on cardiomyocytes and other cell types (11). Apparently, it is the (low abundant) ATP 4 -moiety that binds to receptors, which have been divided into P 1 and P 2 receptors.…”

Section: Discussionmentioning

confidence: 99%

“…On protein level, P 2Y1,4,6,12 and P 2X1,2,3,4,6,7 have been detected in the human heart (3,66). P 2Y1, 2,6,11,12,13 receptors are blocked by either suramin or PPADS or by RB2 (63). Because these antagonists do not block the contractile effects of ATP, this is one argument why P 2Y receptors are not involved.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A positive inotropic effect of ATP in the human cardiac atrium

Gergs¹,

Boknı́k²,

Schmitz³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Gergs U, Boknik P, Schmitz W, Simm A, Silber RE, Neumann J. A positive inotropic effect of ATP in the human cardiac atrium. Am J Physiol Heart Circ Physiol 294: H1716-H1723, 2008. First published February 8, 2008 doi:10.1152/ajpheart.00945.2007.-We studied contractile effects in isolated electrically driven (1 Hz) atrial preparations from patients undergoing cardiac bypass surgery. ATP concentration dependently (10, 30, and 100 M) and rapidly decreased force of contraction (negative inotropic effect, NIE) and thereafter more slowly increased force of contraction. The maximum positive inotropic effect (PIE) at 100 M ATP amounted to 152% of the predrug value (n ϭ 9) and was stable and could be washed out fast and completely. The PIE did not affect time parameters of contraction (time to peak tension and time of relaxation). Moreover, a similar NIE and PIE were noted with adenosine 5Ј-O-(2-thiotriphosphate) (100 M). In contrast 2-methyl-thio-ATP did not exert a NIE but only a PIE. In a second set of experiments, preparations were first incubated for 30 min with purinoreceptor antagonists and, in their continuous presence, 100 M ATP was applied. However, the PIE and NIE of ATP could neither be blocked with suramin (100 and 500 M), pyridoxalphosphate-6-azophenyl-2Ј,4Ј-disulfonic acid (50 M), nor reactive blue 2 (30, 100, and 500 M), which are known blockers for subtypes of P2 receptors, or 1,3-dipropyl-cyclopentvl-xanthine (1 and 10 M), a subtype (A 1 adenosine) P1 receptor blocker. Likewise, the inhibitor of phospholipase C (PLC) activity (U-73122) and the inhibitor of adenylate cyclase activity (SQ-022563) (10 M each) failed to affect the NIE and the PIE of ATP. We tentatively suggest that the PIE of ATP might be mediated via P2X4-like receptors. In summary, we describe a novel biphasic effect of ATP on force contraction in the isolated human atrium. It is conceivable that ATP plays a physiological role in the human heart, for instance, after cardiac injury to sustain contractility. human heart; right atrium; adenosine 5Ј-triphosphate; purinoceptor; inotropy SOON AFTER DISCOVERY of ATP, Drury and Szent-Györgyi reported on cardiac effects of the compound: a negative chronotropic effect and a decrease in blood pressure (19). Berne suggested that the vasodilatory effect of ATP may be mediated by its degradation product adenosine (5). This led to extensive studies on the effects of adenosine in the cardiovascular system. Only later on was interest in ATP itself renewed. This was in part driven by the suggestion that ATP may be a cotransmitter in nonadrenergic and noncholinergic nerves (13). In fact, ATP can be released from nerve terminals as a cotransmitter with norepinephrine and acetylcholine (14).Extracellular ATP was found to exert many effects in the cardiovascular system. These include negative (NIE) and positive (PIE) inotropic effects (species dependent), negative chronotropic and dromotropic as well as antihypertrophic effects (for review, see Ref. 62). A number of additional physiological effects of ATP in ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A positive inotropic effect of ATP in the human cardiac atrium

Gergs¹,

Boknı́k²,

Schmitz³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…higher rate of nucleotide synthesis from adenosine than from either adenine, hypoxanthine, or inosine (Barenkiewicz and Cohen 1980;Bowditch et al 1985;Brown et al 1985;Kolassa et al 1977;Snyder et al 1978;Tully and Sheehan 1980;Zoref-Shani et al 1984); (ii) the preferential conversion of adenosine at low concentrations (< 5 pM) into purine nucleotides and, at high concentrations (>5 pM), its major degradation to inosine (Arch and Newsholme 1978;Peters and Veerkamp 1983;Snyder et al 1978); and (iii) the preferential synthesis of adenine nucleotides from adenine and adenosine (Arch and Newsholme 1978;Barenkiewicz and Cohen 1980;Bowditch et al 1985;Brown et al 1985;Snyder et al 1978;Tully and Sheehan 1980;Zoref-Shani et al 1984). Also common to both aortic and coronary endothelial cells, but not to all mammalian cells, is the metabolic capacity for equal rapid formation of purine nucleotides, mainly adenine nucleotides, from hypoxanthine and inosine (Peters and Veerkamp 1983;Snyder et al 1978;Tully and Sheehan 1980;Zoref-Shani et al 1984).…”

Section: Purine Nucleotide Synthesis In Endothelial Cellsmentioning

confidence: 99%

Purine metabolism in cultured aortic and coronary endothelial cells

C¹,

Nees²,

Gerlach³

1989

Biochem. Cell Biol.

View full text Add to dashboard Cite

Purine salvage pathways in cultured endothelial cells of macrovascular (pig aorta) and microvascular (guinea pig coronary system) origin were investigated by measuring the incorporation of radioactive purine bases (adenine or hypoxanthine) or nucleosides (adenosine or inosine) into purine nucleotides. These precursors were used at initial extracellular concentrations of 0.1, 5, and 500 microM. In both types of endothelial cells, purine nucleotide synthesis occurred with all four substrates. Aortic endothelial cells salvaged adenine best among purines and nucleosides when applied at 0.1 microM. At 5 and 500 microM, adenosine was the best precursor. In contrast, microvascular endothelial cells from the coronary system used adenosine most efficiently at all concentrations studied. The synthetic capacity of salvage pathways was greater than that of the de novo pathway. As measured using radioactive formate or glycine, de novo synthesis of purine nucleotides was barely detectable in aortic endothelial cells, whereas it readily occurred in coronary endothelial cells. Purine de novo synthesis in coronary endothelial cells was inhibited by physiological concentrations of purine bases and nucleosides, and by ribose or isoproterenol. The isoproterenol-induced inhibition was prevented by the beta-adrenergic receptor antagonist propranolol. The end product of purine catabolism in aortic endothelial cells was found to be hypoxanthine, whereas coronary endothelial cells degraded hypoxanthine further to xanthine and uric acid, a reaction catalyzed by the enzyme xanthine dehydrogenase.

show abstract

“…Purine salvage pathway dysfunction due to hypoxic inhibition of adenosine kinase leads to increased extracellular levels of inosine and adenosine in CMs resulting in the activation of mast cells [73,100,101]. Mast cell activation triggers rapid degranulation releasing pre-formed granules containing TNF-α, histamine, tryptase, and chymase [73,74,[102][103][104][105].…”

Section: Mast Cell Activationmentioning

confidence: 99%

Cellular Pathways of Death and Survival in Acute Myocardial Infarction

Kent¹

2013

J Clin Exp Cardiolog

View full text Add to dashboard Cite

During acute myocardial infarction (MI), the cumulative loss of functioning cardiomyocytes (CM) progresses as an imbrication of necrosis, apoptosis, and autophagy. Coronary artery occlusion and subsequent hypoxia causes some CMs to undergo necrosis with most cellular damage occurring near the area of occlusion. The inflammation that ensues plays a critical role in the reparative process and occurs in parallel as CMs struggle to survive. The release of inflammatory pro-apoptotic cytokines compounded with activation of apoptosis results in the programmed death of ischemic CMs. Concurrently, the level of autophagic flux in border zone CMs will determine whether or not these CMs are able to survive hypoxic cellular conditions. The interplay of these processes and the balance that occurs in the peri-infarct area plays a pivotal role in preserving the functional capacity of CMs, specifically through the upregulation of autophagy and downregulation of apoptosis and inflammation. A detailed understanding of these signaling pathways in acute MI is necessary to develop novel therapeutics to promote CM survival and diminish CM death following MI. This review discusses the cellular processes of necrosis, apoptosis, autophagy, and inflammation that occur during acute MI. Also, the common signaling mediators that each process employs and their relationship to each other are discussed to provide a better understanding of these synergistic effects during MI.

show abstract

Accumulation and salvage of adenosine and inosine by isolated mature cardiac myocytes

Cited by 55 publications

References 38 publications

A positive inotropic effect of ATP in the human cardiac atrium

A positive inotropic effect of ATP in the human cardiac atrium

Purine metabolism in cultured aortic and coronary endothelial cells

Cellular Pathways of Death and Survival in Acute Myocardial Infarction

Contact Info

Product

Resources

About