Diinosine pentaphosphate: an antagonist which discriminates between recombinant P2X<sub>3</sub> and P2X<sub>2/3</sub> receptors and between two P2X receptors in rat sensory neurones

Dunn, PM; Liu, M.; Zhong, Yu; King, BF; Burnstock, Geoffrey

doi:10.1038/sj.bjp.0703404

Cited by 59 publications

(55 citation statements)

References 29 publications

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“…DRG of rat and mouse are well studied in regard to the function of P2X receptors (see Dunn et al 2000). ATP depolarizes DRG neurons by eliciting fast-and slow-inactivat- n, number of P2X1-7-or P2Y1,2,4-positive cell profiles and the total number of cell profiles counted.…”

Section: Discussionmentioning

confidence: 99%

Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

Ruan

Birder

Groat

et al. 2005

J Histochem Cytochem.

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S U M M A R YThe distribution of P2X and P2Y receptor subtypes in upper lumbosacral cat dorsal root ganglia (DRG) has been investigated using immunohistochemistry. Intensity of immunoreactivity for six P2X receptors (P2X 5 receptors were immuno-negative) and the three P2Y receptors examined in cat DRG was in the order of P2Y 2 ϭ P2Y 4 Ͼ P2X 3 Ͼ P2X 2 ϭ P2X 7 Ͼ P2X 6 Ͼ P2X 1 ϭ P2X 4 Ͼ P2Y 1 . P2X 3 , P2Y 2 , and P2Y 4 receptor polyclonal antibodies stained 33.8%, 35.3%, and 47.6% of DRG neurons, respectively. Most P2Y 2 , P2X 1 , P2X 3 , P2X 4 , and P2X 6 receptor staining was detected in small-and medium-diameter neurons. However, P2Y 4 , P2X 2 , and P2X 7 staining was present in large-and small-diameter neurons. Doublelabeling immunohistochemistry showed that 90.8%, 32.1%, and 2.4% of P2X 3 receptorpositive neurons coexpressed IB 4 , CGRP, and NF200, respectively; whereas 67.4%, 41.3%, and 39.1% of P2Y 4 receptor-positive neurons coexpressed IB 4 , CGRP, and NF200, respectively. A total of 18.8%, 16.6%, and 63.5% of P2Y 2 receptor-positive neurons also stained for IB 4 , CGRP, and NF200, respectively. Only 30% of DRG neurons in cat were P2X 3 -immunoreactive compared with 90% in rat and in mouse. A further difference was the low expression of P2Y 1 receptors in cat DRG neurons compared with more than 80% of the neurons in rat. Many small-diameter neurons were NF200-positive in cat, again differing from rat and mouse.

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Section: Discussionmentioning

confidence: 99%

Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

Ruan

Birder

Groat

et al. 2005

J Histochem Cytochem.

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“…2Ai). This response has been attributed to the activation of homomeric P2X 3 receptors [Grubb and Evans, 1999;Dunn et al, 2000]. Application of the same concentration of MRS 2312 to these neurones failed to evoke a detectable response.…”

Section: Drg Neuronesmentioning

confidence: 99%

“…Drugs were applied rapidly through a four-or six-barrel manifold [see Dunn et al, 2000]. One barrel was used to apply drug-free solution to enable rapid termination of drug applications.…”

Section: Electrophysiological Recordingmentioning

confidence: 99%

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Northern ring conformation of methanocarba‐adenosine 5′‐triphosphate required for activation of P2X receptors

Dunn

Kim

Burnstock

2004

Drug Development Research

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“…2 It will also be interesting to evaluate 7b at P2X receptors, at which diinosine polyphosphates are potent antagonists. 16 A receptor for guanosine was proposed, 17 based on neuroprotective effects observed for this nucleoside. However, the guanosine analogues here were examined only for interaction with ARs.…”

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confidence: 99%

Synthesis and purine receptor affinity of 6-oxopurine nucleosides and nucleotides containing (N)-methanocarba-pseudoribose rings

Ravi

Lee

et al. 2001

Bioorganic & Medicinal Chemistry Letters

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Abstract6-Oxopurine derivatives containing a northern (N) methanocarba modification (i.e., fused cyclopropane and cyclopentane rings in place of the ribose) were synthesized and the adenosine receptor affinity measured. Guanine or hypoxanthine was coupled at the 7-position, or 1,3-dibutylxanthine was coupled at the 9-position. The pseudoribose ring was also substituted at the 5′-position with an N-methyluronamide or with phosphate groups.We recently examined conformational requirements of the ribose moiety in adenosine derivatives acting as agonists or partial agonists at P2 receptors and at subtypes of adenosine receptors (A 1 , A 2A , and A 3 ARs). 1-3 Using a methanocarba modification originally introduced by Marquez and co-workers, 4 the ribose-like moiety of these derivatives was constrained to either a northern [(N), 2′-exo] or southern [(S), 2′-endo] conformation through fused cyclopropane and cyclopentane rings. Such analogues helped to define the role of ribofuranosyl puckering in stabilizing the active AR-bound conformation, and thereby allowed identification of the (N)-methanocarba conformation as the isomer which preserved affinity at the A 3 and to a lesser extent, A 1 AR. Thus, the (N)-methanocarba analogues, 1 and 2, were highly potent as full agonist (2) 3 or partial agonist (1) at the human A 3 AR. 2 These analogues contained substituent groups known to enhance A 3 affinity in the ribose series [i.e., N 6 -(3-iodobenzyl) and 2-chloro]. The affinity of adenosine methanocarba analogues at the A 2A AR was greatly decreased for the (N)-methanocarba isomer and nearly absent for the (S)-methanocarba isomer.In this study, we combined the (N)-methanocarba modification with known purine receptor ligands containing a 6-oxo-substitution. Among the nucleoside analogues synthesized were derivatives of hypoxanthine, guanosine, and xanthine. For inosine 5,6 and xanthine-7-riboside 7 analogues, a 5′-methyluronamide modification (nucleoside numbering) known to enhance the A 3 AR affinity was included. 3,5 In comparison, xanthine-7-riboside derivatives 3 and 4 bound to and activated the rat A 3 AR with partial or full efficacy, respectively, 7,8 and

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Diinosine pentaphosphate: an antagonist which discriminates between recombinant P2X₃ and P2X_2/3 receptors and between two P2X receptors in rat sensory neurones

Cited by 59 publications

References 29 publications

Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

Northern ring conformation of methanocarba‐adenosine 5′‐triphosphate required for activation of P2X receptors

Synthesis and purine receptor affinity of 6-oxopurine nucleosides and nucleotides containing (N)-methanocarba-pseudoribose rings

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Diinosine pentaphosphate: an antagonist which discriminates between recombinant P2X3 and P2X2/3 receptors and between two P2X receptors in rat sensory neurones

Cited by 59 publications

References 29 publications

Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

Northern ring conformation of methanocarba‐adenosine 5′‐triphosphate required for activation of P2X receptors

Synthesis and purine receptor affinity of 6-oxopurine nucleosides and nucleotides containing (N)-methanocarba-pseudoribose rings

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Diinosine pentaphosphate: an antagonist which discriminates between recombinant P2X₃ and P2X_2/3 receptors and between two P2X receptors in rat sensory neurones