Pharmacological characterization of recombinant human and rat P2X receptor subtypes

Bianchi, Bruce R.; Lynch, Kevin J.; Touma, Edward; Niforatos, Wende; Burgard, Edward C.; Alexander, Karen M.; Park, Helen S; H, Yu; Metzger, Randy E.; Kowaluk, Elizabeth A.; Jarvis, Michael F.; Biesen, Tim van

doi:10.1016/s0014-2999(99)00350-7

Cited by 305 publications

(327 citation statements)

References 39 publications

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“…When monocytes were treated with BzATP (Fig. 3a), a potent activator at both the P2X 1 [26] and P2X 7 [23] receptor, they failed to respond to the subsequent application of NAD + . Presumably, BzATP occupies binding sites such as P2X 1 and/or P2X 7 receptors that are essential for NAD + to exert its effects.…”

Section: Resultsmentioning

confidence: 99%

“…2-MeSATP functions as a potent agonist at the P2X 1 receptors and exhibits modest agonist activity at the P2X 4 and even less activity at the P2X 7 receptor [26].…”

Section: Engagement Of P2x 1 Receptorsmentioning

confidence: 99%

“…To associate a specific P2X receptor subtype with an increase in [Ca 2+ ] i , we used P2X receptor agonists and antagonists, being aware that these substances often lack high selectivity. The inhibition of the NAD + -promoted change in [Ca 2+ ] i by 2-MeSATP, a potent P2X 1 receptor agonist [26], and by suramin, a potent P2X 1 blocker [28], suggested that NAD + interferes with the P2X 1 receptor. The inhibitory effect of the selective P2X 1 antagonist NF449 further underlined a possible role of NAD + as a P2X 1 agonist.…”

Section: Engagement Of P2x 4 Receptorsmentioning

confidence: 99%

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Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

Grahnert

Klein

Hauschildt

2009

Purinergic Signalling

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In the present study, we show that the extracellular addition of nicotinamide adenine dinucleotide (NAD + ) induces a transient rise in [Ca 2+ ] i in human monocytes caused by an influx of extracellular calcium. The NAD + -induced Ca 2+ response was prevented by adenosine triphosphate (ATP), suggesting the involvement of ATP receptors. Of the two subtypes of ATP receptors (P2X and P2Y), the P2X receptors were considered the most likely candidates. By the use of subtype preferential agonists and antagonists, we identified P2X 1 , P2X 4 , and P2X 7 receptors being engaged in the NAD + -induced rise in [Ca 2+ ] i . Among the P2X receptor subtypes, the P2X 7 receptor is unique in facilitating the induction of nonselective pores that allow entry of ethidium upon stimulation with ATP. In monocytes, opening of P2X 7 receptor-dependent pores strongly depends on specific ionic conditions. Measuring pore formation in response to NAD + , we found that NAD + unlike ATP lacks the ability to induce this pore-forming response. Whereas as little as 100 μM ATP was sufficient to activate the nonselective pore, NAD + at concentrations up to 2 mM had no effect. Taken together, these data indicate that despite similarities in the action of extracellular NAD + and ATP there are nucleotide-specific variations. So far, common and distinct features of the two nucleotides are only beginning to be understood.

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Section: Resultsmentioning

confidence: 99%

“…2-MeSATP functions as a potent agonist at the P2X 1 receptors and exhibits modest agonist activity at the P2X 4 and even less activity at the P2X 7 receptor [26].…”

Section: Engagement Of P2x 1 Receptorsmentioning

confidence: 99%

Section: Engagement Of P2x 4 Receptorsmentioning

confidence: 99%

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Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

Grahnert

Klein

Hauschildt

2009

Purinergic Signalling

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“…ATP triggers neuronal excitation through several different subtypes of P2 purinoceptors. ATP is a nonselective agonist with varied potencies for each of the seven ionotropic P2X and eight metabotropic P2Y purinoceptor subtypes currently identified (Ralevic & Burnstock, 1998;Bianchi et al, 1999;Jacobson et al, 2002;Abbracchio et al, 2003). Receptor localization and behavioral studies suggest that more than one of these receptor subtypes is involved in the transmission of peripheral and/or spinal nociceptive signals (Collo et al, 1996;Vulchanova et al, 1996;Cockayne et al, 2000;Souslova et al, 2000;Okada et al, 2002;Yoshida et al, 2002;Tsuda et al, 2003;Wismer et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Effects of A‐317491, a novel and selective P2X₃/P2X_2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration

McGaraughty

Wismer

Zhu

et al. 2003

British J Pharmacology

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169

129

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1 We have recently reported that systemic delivery of A-317491, the first non-nucleotide antagonist that has high affinity and selectivity for blocking P2X 3 homomeric and P2X 2/3 heteromeric channels, is antinociceptive in rat models of chronic inflammatory and neuropathic pain. In an effort to further evaluate the role of P2X 3 /P2X 2/3 receptors in nociceptive transmission, A-317491 was administered either intrathecally or into the hindpaw of a rat in several models of acute and chronic nociception. 2 Intraplantar (ED 50 ¼ 300 nmol) and intrathecal (ED 50 ¼ 30 nmol) injections of A-317491 produced dose-related antinociception in the CFA model of chronic thermal hyperalgesia. Administration of A-317491 by either route was much less effective to reduce thermal hyperalgesia in the carrageenan model of acute inflammatory hyperalgesia. 3 Intrathecal, but not intraplantar, delivery of A-317491 attenuated mechanical allodynia in both the chronic constriction injury and L5-L6 nerve ligation models of neuropathy (ED 50 ¼ 10 nmol for both models). Intrathecal injections of A-317491 did not impede locomotor performance. 4 Both routes of injection were effective in reducing the number of nocifensive events triggered by the injection of formalin into a hindpaw. Nocifensive behaviors were significantly reduced in both the first and second phases of the formalin assay (intrathecal ED 50 ¼ 10 nmol, intraplantar ED 50 4300 nmol). Nocifensive behaviors induced by the P2X receptor agonist a,b-meATP were also significantly reduced by intraplantar injection of A-317491. 5 These data indicate that both spinal and peripheral P2X 3 /P2X 2/3 receptors have significant contributions to nociception in several animal models of nerve or tissue injury. Intrathecal administration of A-317491 appears to be more effective than intraplantar administration to reduce tactile allodynia following peripheral nerve injury.

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“…The response to BzATP in rat retinal ganglion cells was dependent upon extracellular calcium, ruling out G proteinlinked P2Y receptors [19]. The calcium elevation was considerably higher when cells were stimulated by 10 µM BzATP than by 100 µM ATP; the relative potency of BzATP over ATP is a key characteristic of P2X 7 receptors [23,24]. The threefold increase in the response to BzATP upon removal of magnesium is similar to that described for the cloned P2X 7 receptor and rules out a contribution from P2X 5 receptors [20,25].…”

Section: Physiologic Effects Of P2x 7 Receptor Stimulation On Retinalmentioning

confidence: 94%

The P2X7 receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance

Mitchell

et al. 2008

Purinergic Signalling

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Retinal ganglion cells process the visual signal and transmit it along their axons in the optic nerve to the brain. Molecular, immunohistochemical, and functional analyses indicate that the majority of retinal ganglion cells express the ionotropic P2X 7 receptor. Stimulation of the receptor can lead to a rise in intracellular calcium and cell death, although death does not involve the opening of a large diameter pore. Adenosine acting at A 3 receptors can attenuate the rise in calcium and death accompanying P2X 7 receptor activation, suggesting that dephosphorylation of ATP into adenosine is neuroprotective and that the balance of extracellular purines can influence neuronal survival. Increased intraocular pressure can lead to release of excessive extracellular ATP in the retina and damage ganglion cells by acting on P2X 7 receptors, implicating a role for the receptor in the loss of ganglion cell activity in glaucoma. In summary, the activation of P2X 7 receptors has both physiologic and pathophysiologic implications for ganglion cell function. These characteristics may also provide an insight into the contributions the P2X 7 receptor makes to neurons elsewhere.

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Pharmacological characterization of recombinant human and rat P2X receptor subtypes

Cited by 305 publications

References 39 publications

Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

Effects of A‐317491, a novel and selective P2X₃/P2X_2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration

The P2X7 receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance

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Pharmacological characterization of recombinant human and rat P2X receptor subtypes

Cited by 305 publications

References 39 publications

Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

Effects of A‐317491, a novel and selective P2X3/P2X2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration

The P2X7 receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance

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Effects of A‐317491, a novel and selective P2X₃/P2X_2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration