Beta-adrenergic agonists stimulate the oxidative pentose phosphate pathway in the rat heart.

Zimmer, Heinz‐Gerd; Ibel, H.; Suchner, U.

doi:10.1161/01.res.67.6.1525

Cited by 36 publications

(19 citation statements)

References 43 publications

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“…In fact, the isoproterenol-induced prolonged enhancement of cardiac adenine nucleotide biosynthesis appears to be maintained by this elevation in PRPP. 4 Moreover, both isoproterenol3 and NE induced cardiac hypertrophy that could be prevented by 8-adrenergic3 and combined a-and P3-adrenergic'3 blockade, respectively ( Table 2). …”

Section: Resultsmentioning

confidence: 97%

“…13-Adrenergic stimulation with isoproterenol increased cardiac G-6-PD activity, the available PRPP pool, and adenine nucleotide biosynthesis. 4 More recently, a-adrenergic stimulation of the heart has attracted much attention. It has been shown that inositol 1,4,5-trisphosphate (IP3) and diacylglycerol are second messengers7 and that the increase in 1P3 precedes the positive inotropic effect in isolated heart preparations obtained from rats8 and humans.9 Moreover, a-adrenergic stimulation has been identified as one of the possible trigger mechanisms for the induction of myocardial cell growth both in cultured neonatal rat cardiac myocytes10-12 and in rats in vivo.13 ADP UDP 4 4 ATP UTP FIGURE 1.…”

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confidence: 99%

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Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.

Zimmer¹,

Lankat–Buttgereit²,

Kolbeck-Rühmkorff³

et al. 1992

Circulation Research

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To examine whether stimulation of c-adrenergic receptors may affect the oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE) and the c-adrenergic agonist norfenephrine were used. NE was administered as a continuous intravenous infusion in awake rats for 3 days. It stimulated the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the highest dose (0.2 mg * kg`* hr-'), there was also a time-dependent enhancement. The increase observed after 48 hours was attenuated partially by the (3-receptor blocker metoprolol and the a!-receptor blocker prazosin. It was entirely abolished when both drugs were administered. Carvedilol, a j3-adrenergic blocker and vasodilator with eel-blocking activity (0.5 mg * kg`* hr-1), prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio. The ae-adrenergic stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented this stimulation. NE and norfenephrine also elevated the available pool of cardiac 5-phosphoribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac myocytes freshly isolated from the left ventricle of rats that had received NE infusion for 3 days (12.3±1.4 units/g protein) compared with control rats (1.5±0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase, one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7±0.7 to 19.1± 1.4 units/g protein. Combined aand f3-receptor blockade with carvedilol attenuated these effects. Using Northern blot analysis, we showed that G-6-PD mRNA was elevated in a time-dependent manner in hearts of NE-treated rats, reaching a 2.6-fold increase after 3 days. This increase was abolished with carvedilol. The 6-phosphogluconate dehydrogenase mRNA was only slightly and unspecifically enhanced. These results indicate that both crand j3-adrenergic receptors contribute to the stimulation of the oxidative PPP by predominant elevation of G-6-PD mRNA. (Circulation Research 1992;71:451-459) KEY WoRDs * adenine nucleotide metabolism * carvedilol * molecular biology * catecholamines * glucose-6-phosphate dehydrogenase * 6-phosphogluconate dehydrogenase * rat heart function C atecholamines have multiple effects on the function, metabolism, and morphology of the heart. Specifically, stimulation of 83-adrenergic receptors is known to induce a positive chronotropic and inotropic effect, to increase via cAMP glycogenolysis and lipolysis,1 to shift the isomyosin from V3 to the V1 form,2 and to induce cardiac hypertrophy.3 Recently, a new metabolic effect has been found in that f3-adrenergic stimulation increased the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (PPP).4 This pathway is the link between carbohydrate and fatt...

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Section: Resultsmentioning

confidence: 97%

mentioning

confidence: 99%

Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.

Zimmer¹,

Lankat–Buttgereit²,

Kolbeck-Rühmkorff³

et al. 1992

Circulation Research

Self Cite

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“…We show that adrenergic-deficient embryos have decreased G-6-PDH activity, increased ratios of phosphorylated to total G-6-PDH protein, and decreased ribose-5-phosphate, PRPP, and nucleotide concentrations indicating G-6-PDH and PPP are effectively regulated by adrenergic stimulation during embryonic development. Other studies have also shown adrenergic regulation of PPP in working rat hearts exposed to NE and other adrenergic agonists with increased G-6-PDH activity, PRPP concentrations, and adenine nucleotide biosynthesis (59)(60)(61). During development, G-6-PDH has been shown to be protective against oxidative stress resulting from placental circulation and nutrient/respiratory exchange (31,38).…”

Section: Glucose-6-phosphate Dehydrogenase (G-6-pdh)mentioning

confidence: 92%

Metabolomics reveals critical adrenergic regulatory checkpoints in glycolysis and pentose–phosphate pathways in embryonic heart

Peoples

Maxmillian

et al. 2018

Journal of Biological Chemistry

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Cardiac energy demands during early embryonic periods are sufficiently met through glycolysis, but as development proceeds, oxidative phosphorylation in mitochondria becomes increasingly vital. Adrenergic hormones are known to stimulate metabolism in adult mammals and are essential for embryonic development, but relatively little is known about their effects on metabolism in the embryonic heart. Here, we show that embryos lacking adrenergic stimulation have approximately 10-fold less cardiac ATP compared to littermate controls. Despite this deficit in steady-state ATP, neither the rates of ATP formation or degradation were affected in adrenergic-deficient hearts, suggesting that ATP synthesis and hydrolysis mechanisms were fully operational. We thus hypothesized that adrenergic hormones stimulate metabolism of glucose to provide chemical substrates for oxidation in mitochondria. To test this hypothesis, we employed a metabolomics-based approach using liquid chromatography/mass spectrometry (LC/MS). Our results showed glucose-1-phosphate and glucose-6-phosphate concentrations were not significantly altered, but several downstream metabolites in both glycolytic and pentosephosphate pathways were significantly lower compared to controls. Further, we identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glucose-6-phosphate dehydrogenase (G-6-PDH) as key enzymes in those respective metabolic pathways whose activity was significantly (p < 0.05) and substantially (80% and 40%, respectively) lower in adrenergic-deficient hearts.Addition of pyruvate and to a lesser extent, ribose, led to significant recovery of steady-state ATP concentrations. These results demonstrate that without adrenergic stimulation, glucose metabolism in the embryonic heart is severely impaired in multiple pathways, ultimately leading to insufficient metabolic substrate availability for successful transition to aerobic respiration needed for survival.

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“…One study shows that P-adrenergic agonists increase the oxidative pentose phosphate pathway and that the P-adrenergic antagonist atenolol reduces the agonist-induced increase (73). This suggests that propranolol might also have a reducing effect on pentose shunt activity.…”

Section: Saccharomyces Cerevisiae and Candida Uti/is Compared By The mentioning

confidence: 99%

Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

Bolo¹

1991

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Beta-adrenergic agonists stimulate the oxidative pentose phosphate pathway in the rat heart.

Cited by 36 publications

References 43 publications

Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.

Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.

Metabolomics reveals critical adrenergic regulatory checkpoints in glycolysis and pentose–phosphate pathways in embryonic heart

Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

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