The regulation of osteoblast function and bone mineralisation by extracellular nucleotides: The role of p2x receptors

Among the most recently discovered chemical regulators of plant growth and development are extracellular nucleotides, especially extracellular ATP (eATP) and extracellular ADP (eADP). Plant cells release ATP into their extracellular matrix under a variety of different circumstances, and this eATP can then function as an agonist that binds to a specific receptor and induces signaling changes, the earliest of which is an increase in the concentration of cytosolic calcium ([Ca2+]cyt). This initial change is then amplified into downstream-signaling changes that include increased levels of reactive oxygen species and nitric oxide, which ultimately lead to major changes in the growth rate, defense responses, and leaf stomatal apertures of plants. This review presents and discusses the evidence that links receptor activation to increased [Ca2+]cyt and, ultimately, to growth and diverse adaptive changes in plant development. It also discusses the evidence that increased [Ca2+]cyt also enhances the activity of apyrase (nucleoside triphosphate diphosphohydrolase) enzymes that function in multiple subcellular locales to hydrolyze ATP and ADP, and thus limit or terminate the effects of these potent regulators.

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On the Role of ATP-Gated P2X Receptors in Acute, Inflammatory, and Neuropathic Pain

Frontiers in Neuroscience - Translational Pain Research ◽

10.1201/9781439812105-c10 ◽

2009 ◽

Cited By ~ 2

Author(s):

Estelle Toulme ◽

Makoto Tsuda ◽

Baljit Khakh ◽

Kazuhide Inoue

Keyword(s):

Neuropathic Pain ◽

P2x Receptors

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(111) Role of P2X receptors in colon hypersensitivity in the mouse

Journal of Pain ◽

10.1016/j.jpain.2008.01.030 ◽

2008 ◽

Vol 9 (4) ◽

pp. 3 ◽

Cited By ~ 1

Author(s):

M. Shinoda ◽

E. Ohtsuka ◽

G. Gebhart

Keyword(s):

P2x Receptors

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Abstract 2476: Role of retinoblastoma gene in maintenance of osteoblast function and communication

10.1158/1538-7445.am2020-2476 ◽

2020 ◽

Author(s):

Elisha Pendleton ◽

Anthony Ketner ◽

Thomas Bodenstine ◽

Nalini Chandar

Keyword(s):

Retinoblastoma Gene ◽

Osteoblast Function

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Role of the Left Flipper Domain in the Homotrimeric Assembly and Function of P2X Receptors

Biophysical Journal ◽

10.1016/j.bpj.2017.11.721 ◽

2018 ◽

Vol 114 (3) ◽

pp. 127a

Author(s):

Angela Hein ◽

Achim Kless ◽

Ralf Hausmann ◽

Fritz Markwardt ◽

Günther Schmalzing

Keyword(s):

P2x Receptors ◽

And Function

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The Expanding Family of Bone Marrow Homing Factors for Hematopoietic Stem Cells: Stromal Derived Factor 1 Is Not the Only Player in the Game

The Scientific World JOURNAL ◽

10.1100/2012/758512 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 21

Author(s):

Mariusz Z. Ratajczak ◽

ChiHwa Kim ◽

Anna Janowska-Wieczorek ◽

Janina Ratajczak

Keyword(s):

Bone Marrow ◽

Extracellular Nucleotides ◽

Bioactive Lipids ◽

Hematopoietic Stem ◽

Unique Role ◽

Sphingosine 1 Phosphate ◽

Complex Picture ◽

Ceramide 1 ◽

Cxcr4 Axis

Theα-chemokine stromal derived factor 1 (SDF-1), which binds to the CXCR4 and CXCR7 receptors, directs migration and homing of CXCR4+hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) and plays a crucial role in retention of these cells in stem cell niches. However, this unique role of SDF-1 has been recently challenged by several observations supporting SDF-1-CXCR4-independent BM homing. Specifically, it has been demonstrated that HSPCs respond robustly to some bioactive lipids, such as sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), and migrate in response to gradients of certain extracellular nucleotides, including uridine triphosphate (UTP) and adenosine triphosphate (ATP). Moreover, the responsiveness of HSPCs to an SDF-1 gradient is enhanced by some elements of innate immunity (e.g., C3 complement cascade cleavage fragments and antimicrobial cationic peptides, such as cathelicidin/LL-37 orβ2-defensin) as well as prostaglandin E2 (PGE2). Since all these factors are upregulated in BM after myeloblative conditioning for transplantation, a more complex picture of homing emerges that involves several factors supporting, and in some situations even replacing, the SDF-1-CXCR4 axis.

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Activation of P2Y but not P2X4 nucleotide receptors causes elevation of [Ca2+]i in mammalian osteoclasts

AJP Cell Physiology ◽

10.1152/ajpcell.2001.280.6.c1531 ◽

2001 ◽

Vol 280 (6) ◽

pp. C1531-C1539 ◽

Cited By ~ 27

Author(s):

A. Frederik Weidema ◽

S. Jeffrey Dixon ◽

Stephen M. Sims

Keyword(s):

Endoplasmic Reticulum ◽

Patch Clamp ◽

Cyclopiazonic Acid ◽

Cell Types ◽

P2y Receptors ◽

P2x Receptors ◽

Extracellular Nucleotides ◽

Nucleotide Receptors ◽

Inward Current ◽

Store Depletion

Extracellular nucleotides cause elevation of cytosolic free Ca2+ concentration ([Ca2+]i) in osteoclasts, although the sources of Ca2+ are uncertain. Activation of P2Y receptors causes Ca2+ release from stores, whereas P2X receptors are ligand-gated channels that mediate Ca2+ influx in some cell types. To examine the sources of Ca2+, we studied osteoclasts from rat and rabbit using fura 2 fluorescence and patch clamp. Nucleotide-induced rise of [Ca2+]ipersisted on removal of extracellular Ca2+(Ca[Formula: see text]), indicating involvement of stores. Inhibition of phospholipase C (PLC) with U-73122 or inhibition of endoplasmic reticulum Ca2+-ATPase with cyclopiazonic acid or thapsigargin abolished the rise of [Ca2+]i. After store depletion in the absence of Ca[Formula: see text], addition of Ca[Formula: see text] led to a rise of [Ca2+]i consistent with store-operated Ca2+ influx. Store-operated Ca2+ influx was greater at negative potentials and was blocked by La3+. In patch-clamp studies where PLC was blocked, ATP induced inward current indicating activation of P2X4 nucleotide receptors, but with no rise of [Ca2+]i. We conclude that nucleotide-induced elevation of [Ca2+]i in osteoclasts arises primarily through activation of P2Y nucleotide receptors, leading to release of Ca2+ from intracellular stores.

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Role of P2X purinergic receptors in the rescue of ischemic heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00577.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. H1191-H1197 ◽

Cited By ~ 30

Author(s):

Dmitry Sonin ◽

Si-Yuan Zhou ◽

Chunxia Cronin ◽

Tatiana Sonina ◽

Jeffrey Wu ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Infarct Size ◽

Purinergic Receptors ◽

P2x Receptors ◽

Left Ventricular ◽

Ischemic Heart ◽

Post Myocardial Infarction ◽

Ischemic Heart Failure

Evidence is accumulating to support the presence of P2X purinergic receptors in the heart. However, the biological role of this receptor remains to be defined. The objectives here were to determine the role of cardiac P2X receptors in modulating the progression of post-myocardial infarction ischemic heart failure and to investigate the underlying mechanism. The P2X4 receptor (P2X4R) is an important subunit of native cardiac P2X receptors, and the cardiac-specific transgenic overexpression of P2X4R (Tg) was developed as a model. Left anterior descending artery ligation resulted in similar infarct size between Tg and wild-type (WT) mice ( P > 0.1). However, Tg mice showed an enhanced cardiac contractile performance at 7 days, 1 mo, and 2 mo after infarction and an increased survival at 1 and 2 mo after infarction ( P < 0.01). The enhanced intact heart function was manifested by a greater global left ventricular developed pressure and rate of contraction of left ventricular pressure in vitro and by a significantly increased fractional shortening and systolic thickening in the noninfarcted region in vivo ( P < 0.05). The salutary effects on the ischemic heart failure phenotype were seen in both sexes and were not the result of any difference in infarct size in Tg versus WT hearts. An enhanced contractile function of the noninfarcted area in the Tg heart was likely an important rescuing mechanism. The cardiac P2X receptor is a novel target to treat post-myocardial infarction ischemic heart failure.

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