Purinergic receptors expressed in human skeletal muscle fibres

Bornø, Andreas; Ploug, Thorkil; Bune, Laurids T.; Rosenmeier, Jaya B.; Thaning, Pia

doi:10.1007/s11302-011-9279-y

Cited by 21 publications

(22 citation statements)

References 50 publications

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“…Notably, no additive effect of combining L-NA and indomethacin was detected, which is in agreement with NO mediating a part of the prostacyclin-induced vasodilation (33,48). We have previously shown by immunohistochemistry that P 2y 2 receptors are present on capillary endothelial cells (42), whereas other P 2y isoforms, including P 2y 11, appear to be present on skeletal muscle cells (5). The specific role of these receptors in the ATP-induced formation of NO and prostanoids remains to be resolved.…”

Section: Role Of No and Prostanoids In Interstitial Atp-induced Vasodsupporting

confidence: 80%

Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia

Nyberg

Al‐Khazraji

Mortensen

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However, interstitial ATP has solely been described to induce vasoconstriction in skeletal muscle. To examine whether interstitial ATP induces vasodilation in skeletal muscle and to what extent this vasoactive effect is mediated by formation of nitric oxide (NO) and prostanoids, three different experimental models were studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1-10 μM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition of NO and prostanoid formation. Inhibition of these systems abolished the vasodilator effect of ATP. Cell-culture experiments verified ATP-induced formation of NO and prostacyclin in rat skeletal muscle microvascular endothelial cells, and ATP-induced formation of NO in rat skeletal muscle cells. To confirm these findings in humans, ATP was infused into skeletal muscle interstitium of healthy subjects via microdialysis probes and found to increase muscle interstitial concentrations of NO and prostacyclin by ~60% and ~40%, respectively. Collectively, these data suggest that a physiologically relevant elevation in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation.

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Section: Role Of No and Prostanoids In Interstitial Atp-induced Vasodsupporting

confidence: 80%

Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia

Nyberg

Al‐Khazraji

Mortensen

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We investigated the skeletal muscle P2Y2 receptor content, since these receptors appear to be important mediators of ATP-induced vasodilation (34,39). We have previously shown that, in human skeletal muscle, P2Y2 receptors are present in microvascular endothelial and smooth muscle cells with no presence in skeletal muscle cells (4,24), suggesting that the change in skeletal muscle P2Y2 receptor content occurred in the vasculature. However, it is not possible to determine whether the increase in P2Y2 protein occurred specifically in endothelial and/or smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Two weeks of muscle immobilization impairs functional sympatholysis but increases exercise hyperemia and the vasodilatory responsiveness to infused ATP

Mortensen

Mørkeberg

Thaning

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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During exercise, contracting muscles can override sympathetic vasoconstrictor activity (functional sympatholysis). ATP and adenosine have been proposed to play a role in skeletal muscle blood flow regulation. However, little is known about the role of muscle training status on functional sympatholysis and ATP- and adenosine-induced vasodilation. Eight male subjects (22 ± 2 yr, Vo(2max): 49 ± 2 ml O(2)·min(-1)·kg(-1)) were studied before and after 5 wk of one-legged knee-extensor training (3-4 times/wk) and 2 wk of immobilization of the other leg. Leg hemodynamics were measured at rest, during exercise (24 ± 4 watts), and during arterial ATP (0.94 ± 0.03 μmol/min) and adenosine (5.61 ± 0.03 μmol/min) infusion with and without coinfusion of tyramine (11.11 μmol/min). During exercise, leg blood flow (LBF) was lower in the trained leg (2.5 ± 0.1 l/min) compared with the control leg (2.6 ± 0.2 l/min; P < 0.05), and it was higher in the immobilized leg (2.9 ± 0.2 l/min; P < 0.05). Tyramine infusion lowers LBF similarly at rest, but, when tyramine was infused during exercise, LBF was blunted in the immobilized leg (2.5 ± 0.2 l/min; P < 0.05), whereas it was unchanged in the control and trained leg. Mean arterial pressure was lower during exercise with the trained leg compared with the immobilized leg (P < 0.05), and leg vascular conductance was similar. During ATP infusion, the LBF response was higher after immobilization (3.9 ± 0.3 and 4.5 ± 0.6 l/min in the control and immobilized leg, respectively; P < 0.05), whereas it did not change after training. When tyramine was coinfused with ATP, LBF was reduced in the immobilized leg (P < 0.05) but remained similar in the control and trained leg. Training increased skeletal muscle P2Y2 receptor content (P < 0.05), whereas it did not change with immobilization. These results suggest that muscle inactivity impairs functional sympatholysis and that the magnitude of hyperemia and blood pressure response to exercise is dependent on the training status of the muscle. Immobilization also increases the vasodilatory response to infused ATP.

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“…In addition, extracellular ATP stimulates translocation of GLUT4 to plasma membranes of muscle fibres [225]. Exercise increases interstitial concentrations of ATP [226], and a recent study showed immunohistochemical localisation of several P2 receptors on skeletal muscle plasma membrane, and on blood vessels, although the distribution was similar in samples from normal and T2D individuals [227]. …”

Section: Purinergic Signalling In Diabetesmentioning

confidence: 99%

Purinergic signalling and diabetes

Burnstock

Novak

2013

Purinergic Signalling

108

127

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The pancreas is an organ with a central role in nutrient breakdown, nutrient sensing and release of hormones regulating whole body nutrient homeostasis. In diabetes mellitus, the balance is broken—cells can be starving in the midst of plenty. There are indications that the incidence of diabetes type 1 and 2, and possibly pancreatogenic diabetes, is rising globally. Events leading to insulin secretion and action are complex, but there is emerging evidence that intracellular nucleotides and nucleotides are not only important as intracellular energy molecules but also as extracellular signalling molecules in purinergic signalling cascades. This signalling takes place at the level of the pancreas, where the close apposition of various cells—endocrine, exocrine, stromal and immune cells—contributes to the integrated function. Following an introduction to diabetes, the pancreas and purinergic signalling, we will focus on the role of purinergic signalling and its changes associated with diabetes in the pancreas and selected tissues/organ systems affected by hyperglycaemia and other stress molecules of diabetes. Since this is the first review of this kind, a comprehensive historical angle is taken, and common and divergent roles of receptors for nucleotides and nucleosides in different organ systems will be given. This integrated picture will aid our understanding of the challenges of the potential and currently used drugs targeted to specific organ/cells or disorders associated with diabetes.

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Purinergic receptors expressed in human skeletal muscle fibres

Cited by 21 publications

References 50 publications

Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia

Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia

Two weeks of muscle immobilization impairs functional sympatholysis but increases exercise hyperemia and the vasodilatory responsiveness to infused ATP

Purinergic signalling and diabetes

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