Emerging Roles for Ectonucleotidases in Pain-Sensing Neurons

Street, Sarah E.; Zylka, Mark J.

doi:10.1038/npp.2010.141

Cited by 9 publications

(5 citation statements)

References 6 publications

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“…Once ATP or ADP is released, the nucleotide is broken down by nucleoside triphosphate diphosphohydrolases (e.g., CD39) and then ecto‐5′‐nucleotidase (CD73) to adenosine (Fredholm et al, ; Knapp et al, ). The intricacies of localized extracellular release of adenine nucleotides and subsequent production of adenosine following CD73 activity has recently provided insights into the role of adenosine A 1 ‐receptors in mediating localized analgesia in animals and humans (Goldman et al, ; Sowa, Voss, & Zylka, ; Street & Zylka, ). In addition, there is increasing evidence that adenosine A 1 ‐receptors may be involved in promoting angiogenesis and the release of VEGF in response to local hypoxia and neoplasia (Clark et al, ; Merighi et al, ).…”

Section: Introductionmentioning

confidence: 99%

Probe dependence of allosteric enhancers on the binding affinity of adenosine A₁‐receptor agonists at rat and human A₁‐receptors measured using NanoBRET

Cooper

Soave

Jörg

et al. 2019

British J Pharmacology

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Background and Purpose Adenosine is a local mediator that regulates a number of physiological and pathological processes via activation of adenosine A1‐receptors. The activity of adenosine can be regulated at the level of its target receptor via drugs that bind to an allosteric site on the A1‐receptor. Here, we have investigated the species and probe dependence of two allosteric modulators on the binding characteristics of fluorescent and nonfluorescent A1‐receptor agonists. Experimental Approach A Nano‐luciferase (Nluc) BRET (NanoBRET) methodology was used. This used N‐terminal Nluc‐tagged A1‐receptors expressed in HEK293T cells in conjunction with both fluorescent A1‐receptor agonists (adenosine and NECA analogues) and a fluorescent antagonist CA200645. Key Results PD 81,723 and VCP171 elicited positive allosteric effects on the binding affinity of orthosteric agonists at both the rat and human A1‐receptors that showed clear probe dependence. Thus, the allosteric effect on the highly selective partial agonist capadenoson was much less marked than for the full agonists NECA, adenosine, and CCPA in both species. VCP171 and, to a lesser extent, PD 81,723, also increased the specific binding of three fluorescent A1‐receptor agonists in a species‐dependent manner that involved increases in Bmax and pKD. Conclusions and Implications These results demonstrate the power of the NanoBRET ligand‐binding approach to study the effect of allosteric ligands on the binding of fluorescent agonists to the adenosine A1‐receptor in intact living cells. Furthermore, our studies suggest that VCP171 and PD 81,723 may switch a proportion of A1‐receptors to an active agonist conformation (R*).

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Section: Introductionmentioning

confidence: 99%

Probe dependence of allosteric enhancers on the binding affinity of adenosine A₁‐receptor agonists at rat and human A₁‐receptors measured using NanoBRET

Cooper

Soave

Jörg

et al. 2019

British J Pharmacology

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“…Key components of this signaling pathway are (1) adenosine, which is a ligand for multiple adenosine receptors, 1 , 9 , 23 and (2) the transmembrane isoform of prostatic acid phosphatase (PAP), which hydrolyzes extracellular adenosine monophosphate (AMP) into adenosine using its ectonucleotidase properties. 35 , 37 , 47 Prostatic acid phosphatase is widely expressed by nonpeptidergic small-diameter nociceptors 40 , 41 and nerve growth factor (NGF)-dependent peptidergic nociceptors, 41 implying that PAP plays a key role in the maintenance of the delicate balance between nociception and analgesia. Inflammatory pain was alleviated by intrathecal (i.t.)…”

Section: Introductionmentioning

confidence: 99%

Downregulation of adenosine and adenosine A1 receptor contributes to neuropathic pain in resiniferatoxin neuropathy

Kan

Chang

Lin

et al. 2018

Pain

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“…By the control of ATP degradation and adenosine generation, ecto-nucleotidases drive the shift from ATP-induced nociception to adenosine-induced analgesia [97]. Since ATP induces pain and pain sensitization via activation of P2X receptors and adenosine mediates analgesia via activation of P1 receptors, existence of ecto-nucleotidases and their enzymatic activities in the trigeminal nociceptive pathway will affect the development and maintenance of dental orofacial pain.…”

Section: Ecto-nucleotidases In Trigeminal Nerves and Orofacial Painmentioning

confidence: 99%

Purinergic Signaling and Dental Orofacial Pain

Liu¹

2020

Receptors P1 and P2 as Targets for Drug Therapy in Humans

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Pain is a common complaint of patients in the dental clinic. Patient with dental orofacial pain usually presents with hyperalgesia and allodynia. Its management has been a challenge, especially in the status of chronic pain or neuropathic pain. Purinergic signaling is dictated by ATP release, purinergic receptors activation, and sequential hydrolysis of ATP. Purinergic signaling participates in nociception processing in the sensory nerves by control of pain signal transduction, modulation, and sensitization. Since purinergic receptors are preferentially expressed in trigeminal nerves, purinergic singling may play a crucial role in the development of dental orofacial pain. In this chapter, we overview the expressions of purinergic receptors as well as the machinery for ATP release, ATP degradations, and adenosine generation in trigeminal nerves. Specifically, the roles of ATP signaling in dental orofacial pain generation and central sensitization via activation of P2 receptors and adenosine signaling in analgesia via activation of P1 receptors in trigeminal nerves are updated. We also discuss the affection of ecto-nucleotidases, the major enzymes responsible for extracellular ATP degradation and adenosine generation in trigeminal nerves that drive the shift from ATP-induced pain to adenosine-induced analgesia. This chapter provides advanced outlines for purinergic signaling in trigeminal nerves and unveils potential therapeutic targets for the management of dental orofacial pain.

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Emerging Roles for Ectonucleotidases in Pain-Sensing Neurons

Cited by 9 publications

References 6 publications

Probe dependence of allosteric enhancers on the binding affinity of adenosine A₁‐receptor agonists at rat and human A₁‐receptors measured using NanoBRET

Probe dependence of allosteric enhancers on the binding affinity of adenosine A₁‐receptor agonists at rat and human A₁‐receptors measured using NanoBRET

Downregulation of adenosine and adenosine A1 receptor contributes to neuropathic pain in resiniferatoxin neuropathy

Purinergic Signaling and Dental Orofacial Pain

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Emerging Roles for Ectonucleotidases in Pain-Sensing Neurons

Cited by 9 publications

References 6 publications

Probe dependence of allosteric enhancers on the binding affinity of adenosine A1‐receptor agonists at rat and human A1‐receptors measured using NanoBRET

Probe dependence of allosteric enhancers on the binding affinity of adenosine A1‐receptor agonists at rat and human A1‐receptors measured using NanoBRET

Downregulation of adenosine and adenosine A1 receptor contributes to neuropathic pain in resiniferatoxin neuropathy

Purinergic Signaling and Dental Orofacial Pain

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Product

Resources

About

Probe dependence of allosteric enhancers on the binding affinity of adenosine A₁‐receptor agonists at rat and human A₁‐receptors measured using NanoBRET

Probe dependence of allosteric enhancers on the binding affinity of adenosine A₁‐receptor agonists at rat and human A₁‐receptors measured using NanoBRET