Blood cells: an historical account of the roles of purinergic signalling

Burnstock, Geoffrey

doi:10.1007/s11302-015-9462-7

Cited by 64 publications

(64 citation statements)

References 373 publications

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“…31,106 P2Y 1 and P2X7 receptors are the dominant nucleotide receptor subtypes expressed by mature erythrocytes, whereas A 2A receptors are expressed by embryonic red blood cells. ATP is released from human erythrocytes in response to mechanical deformation or hypoxia.…”

Section: Blood Cellsmentioning

confidence: 99%

“…ATP, released as a cotransmitter with noradrenaline from sympathetic nerves, acts on P2X1 receptors to constrict vascular smooth muscle. 31 Increased release of ATP as a sympathetic cotransmitter relative to noradrenaline release in spontaneously hypertensive rats (SHR) has been reported. 155,156 Guanethidine was used in early times for the treatment of hypertension, probably by inhibiting the release of both ATP and noradrenaline from sympathetic nerves.…”

Section: Vascular Diseasesmentioning

confidence: 99%

“…30 The involvement of purinergic signaling in the biology of erythrocytes, platelets, and leukocytes was recognized early and an account is included of later studies leading to our current understanding of the various roles played by purine nucleotides and nucleosides in health and disease. 31 There is also a valuable earlier review about the roles of nucleotide receptors in blood cells. 32 Information is reviewed about purinergic peripheral and central nervous control of the vascular system.…”

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confidence: 99%

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Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

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317

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Abstract:There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y 1 , P2Y 12 , and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine. (Circ Res. 2017;120:207-228.

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Section: Blood Cellsmentioning

confidence: 99%

Section: Vascular Diseasesmentioning

confidence: 99%

mentioning

confidence: 99%

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Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

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317

295

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“…P2Y receptors modulate several signaling events including adenylyl cyclase, phospholipase C, and ion channel activation [16,18]. P2 receptors are present on all blood cells [19]. It is reported that some pore-forming toxins require purinergic signaling to elicit their toxicity [16].…”

Section: Introductionmentioning

confidence: 99%

Hemolysis in human erythrocytes by Clostridium perfringens epsilon toxin requires activation of P2 receptors

et al. 2018

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Epsilon-toxin (ETX) is produced by types B and D strains of Clostridium perfringens, which cause fatal enterotoxaemia in sheep, goats and cattle. Previous studies showed that only a restricted number of cell lines are sensitive to ETX and ETX-induced hemolysis has not previously been reported. In this study, the hemolytic ability of ETX was examined using erythrocytes from 10 species including murine, rabbit, sheep, monkey and human. We found that ETX caused hemolysis in human erythrocytes (HC50 = 0.2 μM) but not erythrocytes from the other test species. Moreover, the mechanism of ETX-induced hemolysis was further explored. Recent studies showed that some bacterial toxins induce hemolysis through purinergic receptor (P2) activation. Hence, the function of purinergic receptors in ETX-induced hemolysis was tested, and we found that the non-selective P2 receptor antagonists PPADS inhibited ETX-induced lysis of human erythrocytes in a concentration-dependent manner, indicating that ETX-induced hemolysis requires activation of purinergic receptors. P2 receptors comprise seven P2X (P2X1–7) and eight P2Y (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11–P2Y14) receptor subtypes. The pattern of responsiveness to more selective P2-antagonists implies that both P2Y13 and P2X7 receptors are involved in ETX-induced hemolysis in human species. Furthermore, we demonstrated that extracellular ATP is likely not involved in ETX-induced hemolysis and the activation of P2 receptors. These findings clarified the mechanism of ETX-induced hemolysis and provided new insight into the activities and ETX mode of action.

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“…Neurotransmission, secretion, transduction, cell proliferation, motility, and differentiation are typical examples of biological functions modulated by nucleotides or nucleosides acting as extracellular signaling molecules [5][6][7][8][9][10][11]. Burnstock's early hypothesis that ATP, the major intracellular molecule providing the energy required for multiple biochemical and biophysical processes, may actually function as an extracellular non-adrenergic and noncholinergic signaling molecule [12,13] was received with great skepticism [14,15].…”

Section: Introductionmentioning

confidence: 99%

Purinergic control of lysenin’s transport and voltage-gating properties

Bryant

Shrestha

Carnig

et al. 2016

Purinergic Signalling

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Lysenin, a pore-forming protein extracted from the coelomic fluid of the earthworm Eisenia foetida, manifests cytolytic activity by inserting large conductance pores in host membranes containing sphingomyelin. In the present study, we found that adenosine phosphates control the biological activity of lysenin channels inserted into planar lipid membranes with respect to their macroscopic conductance and voltage-induced gating. Addition of ATP, ADP, or AMP decreased the macroscopic conductance of lysenin channels in a concentration-dependent manner, with ATP being the most potent inhibitor and AMP the least. ATP removal from the bulk solutions by buffer exchange quickly reinstated the macroscopic conductance and demonstrated reversibility. Singlechannel experiments pointed to an inhibition mechanism that most probably relies on electrostatic binding and partial occlusion of the channel-conducting pathway, rather than ligand gating induced by the highly charged phosphates. The Hill analysis of the changes in macroscopic conduction as a function of the inhibitor concentration suggested cooperative binding as descriptive of the inhibition process. Ionic screening significantly reduced the ATP inhibitory efficacy, in support of the electrostatic binding hypothesis. In addition to conductance modulation, purinergic control over the biological activity of lysenin channels has also been observed to manifest as changes of the voltage-induced gating profile. Our analysis strongly suggests that not only the inhibitor's charge but also its ability to adopt a folded conformation may explain the differences in the observed influence of ATP, ADP, and AMP on lysenin's biological activity.

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Blood cells: an historical account of the roles of purinergic signalling

Cited by 64 publications

References 373 publications

Purinergic Signaling in the Cardiovascular System

Purinergic Signaling in the Cardiovascular System

Hemolysis in human erythrocytes by Clostridium perfringens epsilon toxin requires activation of P2 receptors

Purinergic control of lysenin’s transport and voltage-gating properties

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