Adenosine stimulates glycolytic flux in isolated perfused rat hearts by A1-adenosine receptors

Wyatt, David A.; Edmunds, Meade C.; Rubio, Rafael; Berne, Robert M.; Lasley, Robert D.; Mentzer, Robert M.

doi:10.1152/ajpheart.1989.257.6.h1952

Cited by 53 publications

(38 citation statements)

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“…However, the way by which A 1 R might impact on metabolism is still poorly characterised. For instance the cardioprotective effect of adenosine is related to the ability of A 1 R activation to control glucose and glycogen metabolism [168][169][170][171]. Adenosine also affects both brain neuronal and astrocytic intermediary metabolism [63,[172][173][174][175][176].…”

Section: B Possible Mechanisms Operated By a 1 Receptors To Manage mentioning

confidence: 99%

Role of The Purinergic Neuromodulation System in Epilepsy

Tomé¹,

Silva²,

Cunha³

2010

TONEURJ

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Adenosine has long been considered an endogenous anti-epileptic compound. This concept was based on the widespread distribution of adenosine A 1 receptors (A 1 R), which are mostly located in excitatory synapses; here, A 1 R inhibit glutamate release, decrease glutamatergic responsiveness and hyperpolarise neurons. However, the combined observation that synaptic A 1 R undergo desensitisation in chronic noxious situations whereas the activation of A 1 R still prevents seizure activity suggests that the A 1 R anti-epileptic action may involve non-synaptic mechanisms. Two alternative mechanisms can be considered to explain the ability of A 1 R to control seizure activity and resulting neurodegeneration: 1) the possible role of A 1 R-mediated control of metabolism; 2) the A 1 R-mediated preconditioning involving a coordinated control of neuron-glia communication. However, purinergic modulation of seizure activity is likely to involve other systems apart from A 1 R. Thus, the blockade of adenosine A 2A receptors (A 2A R), which density increases in animal models of epilepsy, can attenuate seizure activity and prevent seizure-induced neurodegeneration. Furthermore, ATP, which is the main source of the endogenous adenosine activating A 2A R, also act as a general danger signal and may also directly control seizure activity through P 2 receptors (P 2 R). Therefore, the purinergic control of epilepsy may actually involve different parallel signalling arms, some beneficial and others deleterious, probably acting at different sites (in epileptic foci and in their neighbourhood) and at different times. It is likely that combined targeting of different purinergic receptors may be the most efficacious way to control seizure activity, its spreading and the resulting neurodegeneration.

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Section: B Possible Mechanisms Operated By a 1 Receptors To Manage mentioning

confidence: 99%

Role of The Purinergic Neuromodulation System in Epilepsy

Tomé¹,

Silva²,

Cunha³

2010

TONEURJ

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“…Over all, mean fetal glucose levels in the hour of normoxia with A 1 receptor blockade increased by ϳ14% over control values, which would have been even greater had insulin concentrations not also risen concomitantly by ϳ22%. A 1 receptors suppress glycemia by facilitating glucose deposition through enhancement of GLUT4 capacity and promotion of glucose utilization in adult tissues (1,6,14,34,53); and these mechanisms are likely involved in lowering fetal glucose concentrations.…”

Section: Glucosementioning

confidence: 99%

“…Hypoxia also lowers fetal plasma concentrations of insulin, while it raises levels of glucose and lactate (22,26). Adenosine, via the A 1 receptor, facilitates glycolysis in normoxic adult tissues in vitro (53); thus, adenosine may also be involved in fetal metabolic responses to acute O 2 deficiency (25). This study was designed to test the hypothesis that adenosine (ADO) A 1 and A 2A receptors participate in the regulation of fetal plasma concentrations of insulin, glucose, and lactate under both normoxic and hypoxic conditions.…”

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confidence: 99%

Adenosine A₁ and A_2a receptors modulate insulinemia, glycemia, and lactatemia in fetal sheep

Maeda¹,

Koos²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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A 1 and A2A receptor subtypes modulate metabolism in adult mammals. This study was designed to determine the role of these receptors in regulating plasma levels of insulin, glucose, and lactate in 20 chronically catheterized fetal sheep (Ͼ0.8 term). In normoxic fetuses (Pa O 2 ϳ24 Torr), systemic blockade of A1 receptors with DPCPX (n ϭ 6) increased plasma concentrations of insulin, glucose, and lactate, but antagonism of A 2A receptors with ZM-241385 (n ϭ 5) had no significant effects. Intravascular administration of adenosine (n ϭ 9) reduced insulin concentrations and elevated glucose and lactate levels. DPCPX (n ϭ 6) augmented the glycemic and lactatemic responses of adenosine. In contrast, ZM241385 (n ϭ 5) virtually abolished adenosine-induced hyperglycemia and hyperlactatemia. Isocapnic hypoxia (Pa O 2 ϳ13 Torr) suppressed insulinemia and enhanced glycemia and lactatemia, but only the hyperglycemia was blunted by blockade of A1 (n ϭ 6) or A2A (n ϭ 6) receptors. We conclude that 1) endogenous adenosine via A1 receptors depresses plasma concentrations of insulin, glucose, and lactate; 2) exogenous adenosine via A2A receptors increases glucose and lactate levels, but these responses are dampened by stimulation of A1 receptors; and 3) hypoxia, which increases endogenous adenosine concentrations, induces hyperglycemia that is partly mediated by activation of A1 and A2A receptors. We predict that adenosine, via A1 receptors, facilitates at least 12% of glucose uptake and utilization in normoxic fetuses. fetus; hypoxia; metabolism; growth; placenta ADENOSINE REGULATES GLUCOSE metabolism in mammals through several mechanisms that include inhibiting insulin secretion by islet cells, altering insulin transduction, and facilitating intracellular glucose transport. Interstitial levels of adenosine increase substantially in hypoxia, hypoglycemia, or heightened cellular metabolism that can occur through intense neuronal activity or skeletal muscle contractions. The physiological effects of adenosine are mediated through activation of G protein-liganded cell surface receptors that are subdivided into four adenosine receptor subtypes: A 1 , A 2A , A 2B , and A 3 (45). These receptors are connected to classical second-messenger pathways that modulate intracellular cAMP production, phospholipase C pathway, and mitogen-activated protein kinases (45,46). With regard to cAMP, stimulation of A 1 receptors, via inhibition of adenylyl cyclase, generally inhibits intracellular cAMP synthesis, while activation of A 2A and A 2B receptors has the opposite effects.Glucose promotes A 1 and A 2A expression in rat cardiac fibroblasts, while insulin suppresses the expression of A 1 and A 2B receptors (11). Insulin also facilitates the equilibrative transcellular movement of adenosine through stimulation of nucleoside transporters in human umbilical vein endothelial cells (37). Adenosine, in turn, inhibits insulin release via activation of islet A 1 receptors (21, 51). Stimulation of A 1 receptors also enhances glucose uptake in tissues thr...

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“…Adenosine has been shown to inhibit neutrophil oxidative metabolism and adhesion to endothelial cells, to increase membrane stability and energy production by promoting glucose transport, and to reduce Ca 2ϩ influx through the activation of ATP-dependent K ϩ channels [72][73][74][75]. However, the role of all biochemical effects in adenosine-afforded protection is yet to be defined.…”

Section: Protective Mechanisms Of Early Ischemic Preconditioningmentioning

confidence: 99%

Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning

Cutrn

Perrelli

Cavalieri

et al. 2002

Free Radical Biology and Medicine

150

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Abstract-Hepatic ischemia/reperfusion injury has immediate and deleterious effects on the outcome of patients after liver surgery. The precise mechanisms leading to the damage have not been completely elucidated. However, there is substantial evidence that the generation of oxygen free radicals and disturbances of the hepatic microcirculation are involved in this clinical syndrome. Microcirculatory dysfunction of the liver seems to be mediated by sinusoidal endothelial cell damage and by the imbalance of vasoconstrictor and vasodilator molecules, such as endothelin (ET), reactive oxygen species (ROS), and nitric oxide (NO). This may lead to no-reflow phenomenon with release of proinflammatory cytokines, sinusoidal plugging of neutrophils, oxidative stress, and as an ultimate consequence, hypoxic cell injury and parenchymal failure. An inducible potent endogenous mechanism against ischemia/reperfusion injury has been termed ischemic preconditioning. It has been suggested that preconditioning could inhibit the effects of different mediators involved in the microcirculatory dysfunction, including endothelin, tumor necrosis factor-␣, and oxygen free radicals. In this review, we address the mechanisms of liver microcirculatory dysfunction and how ischemic preconditioning could help to provide new surgical and/or pharmacological strategies to protect the liver against reperfusion damage.

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Adenosine stimulates glycolytic flux in isolated perfused rat hearts by A1-adenosine receptors

Cited by 53 publications

References 0 publications

Role of The Purinergic Neuromodulation System in Epilepsy

Role of The Purinergic Neuromodulation System in Epilepsy

Adenosine A₁ and A_2a receptors modulate insulinemia, glycemia, and lactatemia in fetal sheep

Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning

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Adenosine stimulates glycolytic flux in isolated perfused rat hearts by A1-adenosine receptors

Cited by 53 publications

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Role of The Purinergic Neuromodulation System in Epilepsy

Role of The Purinergic Neuromodulation System in Epilepsy

Adenosine A1 and A2a receptors modulate insulinemia, glycemia, and lactatemia in fetal sheep

Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning

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Product

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Adenosine A₁ and A_2a receptors modulate insulinemia, glycemia, and lactatemia in fetal sheep