Cloning and functional expression of a brain G‐protein‐coupled ATP receptor

Webb, Tania E.; Simon, József; Krishek, Belinda J.; Bateson, Alan N.; Smart, Trevor G.; King, Brian F.; Burnstock, Geoffrey; Barnard, Eric A.

doi:10.1016/0014-5793(93)81397-i

Cited by 513 publications

(355 citation statements)

References 28 publications

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“…In 1993, the first receptors for nucleotides, called P2 purinoceptors, were cloned46, 47. Afterwards, numerous subtypes of these receptors were also cloned, and subsequently scientists began to gradually accept the ‘purinergic system.’ Now purinergic P2 receptors are divided into two families, ionotropic receptors (P2X) and metabotropic receptors (P2Y).…”

Section: Spinal Microglia Are Crucial For Neuropathic Painmentioning

confidence: 99%

Microglia in the spinal cord and neuropathic pain

Tsuda

2015

J of Diabetes Invest

217

147

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In contrast to physiological pain, pathological pain is not dependent on the presence of tissue‐damaging stimuli. One type of pathological pain – neuropathic pain – is often a consequence of nerve injury or of diseases such as diabetes. Neuropathic pain can be agonizing, can persist over long periods and is often resistant to known painkillers. A growing body of evidence shows that many pathological processes within the central nervous system are mediated by complex interactions between neurons and glial cells. In the case of painful peripheral neuropathy, spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. After nerve damage, purinergic P2X4 receptors (non‐selective cation channels activated by extracellular adenosine triphosphate) are upregulated in spinal microglia in a manner that depends on the transcription factors interferon regulatory factor 8 and 5, both of which are expressed in microglia after peripheral nerve injury. P2X4 receptor expression on the cell surface of microglia is also regulated at the post‐translational level by signaling from CC chemokine receptor chemotactic cytokine receptor 2. Furthermore, spinal microglia in response to extracellular stimuli results in signal transduction through intracellular signaling cascades, such as mitogen‐activated protein kinases, p38 and extracellular signal‐regulated protein kinase. Importantly, inhibiting the function or expression of these microglial molecules suppresses the aberrant excitability of dorsal horn neurons and neuropathic pain. These findings show that spinal microglia are a central player in mechanisms for neuropathic pain, and might be a potential target for treating the chronic pain state.

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Section: Spinal Microglia Are Crucial For Neuropathic Painmentioning

confidence: 99%

Microglia in the spinal cord and neuropathic pain

Tsuda

2015

J of Diabetes Invest

217

147

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“…This classification has recently been expanded (Abbracchio and Burnstock, 1994;Barnard et al, 1994) to accommodate the results of cloning studies that revealed the existence of multiple subclasses of P2y purinoceptors Webb et al, 1993;Parr et al, 1994). Activation of the two major subclasses of G-proteincoupled receptors, P2Y(P2Y1) and P2U(P2Y2)' results in phospholipase C-catalysed hydrolysis of phosphatidylinositol 4,5-bisphosphate and consequent inositol 1,4,5-trisphosphate-mediated release of calcium from intracellular stores (Boarder et al, 1995).…”

mentioning

confidence: 99%

Extracellular nucleotides stimulate proliferation in MCF-7 breast cancer cells via P2-purinoceptors

Dixon

Wb²,

Fleetwood³

et al. 1997

Br J Cancer

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“…In freshly dissociated limb cells, large increases in [Ca 2ϩ ] i were elicited by ATP, ADP, and 2MeSATP (a synthetic analogue of ATP that is a potent agonist of the recombinant cP2Y 1 receptor expressed in Xenopus oocytes, Webb et al, 1993;Simon et al, 1995) at concentrations of 100 M and 10 M. Figure 2 shows typical [Ca 2ϩ ] i increases in single cells or small clusters of cells to these nucleotides. A small Ca 2ϩi transient was also detected in response to 100 M UTP (Fig.…”

Section: Monitoring Intracellular Free Calcium Levels Demonstrates Thmentioning

confidence: 99%

“…P2X receptors are members of the ligand-gated ion channel superfamily, whereas P2Y receptors constitute a family of G protein-coupled receptors for extracellular nucleotides. Activation of the P2Y receptor cP2Y 1 by extracellular ATP leads to mobilization of intracellular calcium (Ca 2ϩi ) and activation of protein kinase C (PKC) (Webb et al, 1993;Simon et al, 1995). Mobilization of Ca 2ϩi , and the cascade of intracellular protein phosphorylation initiated by activation of PKC, are important regulators of cell growth and differentiation (Berridge, 1993;Lauder, 1993), and there is now considerable evidence supporting a role for P2Y receptor signaling in regulating long-term changes in cell proliferation and differentiation (reviewed in Abbracchio, 1996;Neary and Burnstock, 1996).…”

Section: Introductionmentioning

confidence: 99%

The extracellular ATP receptor, cP2Y₁, inhibits cartilage formation in micromass cultures of chick limb mesenchyme

Meyer

Swann

Burnstock

et al. 2001

Developmental Dynamics

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We have investigated the function of the G protein-coupled receptor for extracellular ATP, chick P2Y 1 (cP2Y 1 ) during development of the chick limb. cP2Y 1 is strongly expressed in undifferentiated limb mesenchyme cells but appears to be lost from cells as they differentiate, raising the possibility that the function of this receptor may be to inhibit cell differentiation. This pattern of expression was particularly striking surrounding areas of cartilage formation. We tested whether cP2Y 1 was able to regulate cartilage formation by using an in-vitro micromass model of chondrogenesis. Because limb cells in micromass culture lose expression of cP2Y 1 , we have used a gain-of-function approach to demonstrate that cP2Y 1 expression can inhibit cartilage differentiation. We also demonstrate that early limb mesenchyme cells release ATP into the extracellular medium and have mechanisms to breakdown extracellular ATP. These results suggest that extracellular ATP, signaling through cP2Y 1 , can modulate the differentiation of limb mesenchyme cells in vitro, and the expression pattern of cP2Y 1 suggests that this type of signaling could play a similar role in ovo.

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Cloning and functional expression of a brain G‐protein‐coupled ATP receptor

Cited by 513 publications

References 28 publications

Microglia in the spinal cord and neuropathic pain

Microglia in the spinal cord and neuropathic pain

Extracellular nucleotides stimulate proliferation in MCF-7 breast cancer cells via P2-purinoceptors

The extracellular ATP receptor, cP2Y₁, inhibits cartilage formation in micromass cultures of chick limb mesenchyme

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Cloning and functional expression of a brain G‐protein‐coupled ATP receptor

Cited by 513 publications

References 28 publications

Microglia in the spinal cord and neuropathic pain

Microglia in the spinal cord and neuropathic pain

Extracellular nucleotides stimulate proliferation in MCF-7 breast cancer cells via P2-purinoceptors

The extracellular ATP receptor, cP2Y1, inhibits cartilage formation in micromass cultures of chick limb mesenchyme

Contact Info

Product

Resources

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The extracellular ATP receptor, cP2Y₁, inhibits cartilage formation in micromass cultures of chick limb mesenchyme