2′,3′‐O‐(2,4,6‐ trinitrophenyl) adenosine 5′‐triphosphate (TNP‐ATP)–a nanomolar affinity antagonist at rat mesenteric artery P2X receptor ion channels

Lewis, Carolyn J.; Surprenant, Annmarie; Evans, Richard J.

doi:10.1038/sj.bjp.0702001

Cited by 80 publications

(72 citation statements)

References 14 publications

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“…Rapidly desensitizing current responses to both ATP and the selective P2X 1,3 agonist a,b-meATP (Ralevic and Burnstock 1998) were observed as a characteristic feature of homomeric P2X 3 receptors (Lewis et al 1995). Furthermore, the P2X 1,3 receptor antagonist TNP-ATP (Lewis et al 1998) and the P2X 1,2,3 preferential antagonist PPADS (Lambrecht 2000) markedly inhibited the effect of a,b-meATP. A few experiments were aimed at clarifying why the concentration-response curve for a,b-meATP had a higher maximum than that for ATP itself.…”

Section: Discussionmentioning

confidence: 99%

Characterization of P2X₃, P2Y₁ and P2Y₄ receptors in cultured HEK293‐hP2X₃ cells and their inhibition by ethanol and trichloroethanol

Fischer¹,

Wirkner²,

Weber

et al. 2003

Journal of Neurochemistry

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Membrane currents and changes in the intracellular Ca ] i was observed after the slow superfusion of ATP, ADPb-S and UTP; a,b-meATP was ineffective. These data, in conjunction with results obtained by using the P2 receptor antagonists TNP-ATP, PPADS and MRS2179 indicate that the current response to a,b-meATP is due to P2X 3 receptor activation, while the ATP-induced rise in [Ca 2+ ] i is evoked by P2Y 1 and P2Y 4 receptor activation. TCE depressed the a,b-meATP current in a manner compatible with a non-competitive antagonism. The ATP-induced increase of [Ca 2+ ] i was much less sensitive to the inhibitory effect of TCE than the current response to a,b-meATP. The present study indicates that in HEK293-hP2X 3 cells, TCE, but not ethanol, potently inhibits ligand-gated P2X 3 receptors and, in addition, moderately interferes with G protein-coupled P2Y 1 and P2Y 4 receptors. Such an effect may be relevant for the interruption of pain transmission in dorsal root ganglion neurons following ingestion of chloral hydrate or trichloroethylene.

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Section: Discussionmentioning

confidence: 99%

Characterization of P2X₃, P2Y₁ and P2Y₄ receptors in cultured HEK293‐hP2X₃ cells and their inhibition by ethanol and trichloroethanol

Fischer¹,

Wirkner²,

Weber

et al. 2003

Journal of Neurochemistry

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“…6b, d, f, h). The selective P2X receptor antagonist TNP-ATP [42,43] did not exert any significant effect on cardiac gene expression, indicating that P2X receptors may not be involved in stem cell differentiation toward cardiomyocytes (data not shown).…”

Section: Inhibition Of Cardiac-specific Gene Expression Upon Pharmacomentioning

confidence: 95%

Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

Mazrouei

Sharifpanah

Bekhite

et al. 2015

Purinergic Signalling

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Purinergic signaling may be involved in embryonic development of the heart. In the present study, the effects of purinergic receptor stimulation on cardiomyogenesis of mouse embryonic stem (ES) cells were investigated. ADP or ATP increased the number of cardiac clusters and cardiac cells, as well as beating frequency. Cardiac-specific genes showed enhanced expression of α-MHC, MLC2v, α-actinin, connexin 45 (Cx45), and HCN4, on both gene and protein levels upon ADP/ATP treatment, indicating increased cardiomyogenesis and pacemaker cell differentiation. Real-time RT-PCR analysis of purinergic receptor expression demonstrated presence of P2X1, P2X4, P2X6, P2X7, P2Y1, P2Y2, P2Y4, and P2Y6 on differentiating ES cells. ATP and ADP as well as the P2X agonists β,γ-methylenadenosine 5′-triphosphate (β,γ-MetATP) and 8-bromoadenosine 5′-triphosphate (8- Br

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“…Analgesic pharmacology and drug-like properties of P2X receptor antagonists P2X3 receptors Table 3 onists that have been studied in a wide variety of animal pain models [8,[26][27][28][29][30][31]. The utility of these antagonists for delineating mechanistically specific contributions of individual P2X receptors to pain is limited by their nonselective pharmacology and generally weak potency [10].…”

Section: Gabapentinmentioning

confidence: 99%

“…2′(3′)-O-(2,4,6-Trinitrophenyl) ATP (TNP-ATP; compound 1) is a nonselective but highly potent antagonist of P2X1 receptors and P2X3 receptors [9,29]. The ability to use this antagonist for preclinical pain studies in rodents is limited by its poor metabolic stability in plasma [30].…”

Section: Gabapentinmentioning

confidence: 99%

P2X receptor antagonists for pain management: examination of binding and physicochemical properties

Gum

Wakefield

Jarvis

2011

Purinergic Signalling

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Enhanced sensitivity to noxious stimuli and the perception of non-noxious stimuli as painful are hallmark sensory perturbations associated with chronic pain. It is now appreciated that ATP, through its actions as an excitatory neurotransmitter, plays a prominent role in the initiation and maintenance of chronic pain states. Mechanistically, the ability of ATP to drive nociceptive sensitivity is mediated through direct interactions at neuronal P2X3 and P2X2/3 receptors. Extracellular ATP also activates P2X4, P2X7, and several P2Y receptors on glial cells within the spinal cord, which leads to a heightened state of neural-glial cell interaction in ongoing pain states. Following the molecular identification of the P2 receptor superfamilies, selective small molecule antagonists for several P2 receptor subtypes were identified, which have been useful for investigating the role of specific P2X receptors in preclinical chronic pain models. More recently, several P2X receptor antagonists have advanced into clinical trials for inflammation and pain. The development of orally bioavailable blockers for ion channels, including the P2X receptors, has been traditionally difficult due to the necessity of combining requirements for target potency and selectivity with suitable absorption distribution, metabolism, and elimination properties. Recent studies on the physicochemical properties of marketed orally bioavailable drugs, have identified several parameters that appear critical for increasing the probability of achieving suitable bioavailability, central nervous system exposure, and acceptable safety necessary for clinical efficacy. This review provides an overview of the antinociceptive pharmacology of P2X receptor antagonists and the chemical diversity and drug-like properties for emerging antagonists of P2X3, P2X2/3, P2X4, and P2X7 receptors. Keywords

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2′,3′‐O‐(2,4,6‐ trinitrophenyl) adenosine 5′‐triphosphate (TNP‐ATP)–a nanomolar affinity antagonist at rat mesenteric artery P2X receptor ion channels

Cited by 80 publications

References 14 publications

Characterization of P2X₃, P2Y₁ and P2Y₄ receptors in cultured HEK293‐hP2X₃ cells and their inhibition by ethanol and trichloroethanol

Characterization of P2X₃, P2Y₁ and P2Y₄ receptors in cultured HEK293‐hP2X₃ cells and their inhibition by ethanol and trichloroethanol

Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

P2X receptor antagonists for pain management: examination of binding and physicochemical properties

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2′,3′‐O‐(2,4,6‐ trinitrophenyl) adenosine 5′‐triphosphate (TNP‐ATP)–a nanomolar affinity antagonist at rat mesenteric artery P2X receptor ion channels

Cited by 80 publications

References 14 publications

Characterization of P2X3, P2Y1 and P2Y4 receptors in cultured HEK293‐hP2X3 cells and their inhibition by ethanol and trichloroethanol

Characterization of P2X3, P2Y1 and P2Y4 receptors in cultured HEK293‐hP2X3 cells and their inhibition by ethanol and trichloroethanol

Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

P2X receptor antagonists for pain management: examination of binding and physicochemical properties

Contact Info

Product

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Characterization of P2X₃, P2Y₁ and P2Y₄ receptors in cultured HEK293‐hP2X₃ cells and their inhibition by ethanol and trichloroethanol

Characterization of P2X₃, P2Y₁ and P2Y₄ receptors in cultured HEK293‐hP2X₃ cells and their inhibition by ethanol and trichloroethanol