PPADS: an antagonist at endothelial P<sub>2Y</sub>‐purinoceptors but not P<sub>2U</sub>‐purinoceptors

Brown, Colin B.; Tanna, Bhavna; Boarder, Michael R.

doi:10.1111/j.1476-5381.1995.tb15088.x

Cited by 64 publications

(51 citation statements)

References 20 publications

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“…In addition, PPADS has been suggested to be a useful tool to distinguish between P2y-and P2u-purinoceptor-mediated responses. In bovine aortic endothelial cells, PPADS inhibits the action of selective agonists of P2Y-purinoceptors (adenosine 5'-diphosphate (ADP) and 2-methylthio ATP) on phospholipase C activity; it did not inhibit the actions of agonists of P2U-purinoceptors (Brown et al, 1995). However, different results have been obtained in astrocytes from the dorsal spinal cord of the rat (Ho et al, 1995).…”

Section: Introductionmentioning

confidence: 71%

“…Its interaction with P2u-purinoceptors is less clear. In aortic endothelial cells, PPADS did not inhibit UTP-induced activation of phospholipase C and it was suggested to be a selective antagonist of P2YI-purinoceptor responses (Brown et al, 1995). In astrocytes from the dorsal spinal cord of the rat, PPADS inhibited UTP-induced changes in [Ca2+]i (Ho et al, 1995).…”

Section: Methodsmentioning

confidence: 99%

“…Time (min) Figure 5 The lack of an effect of PPADS on ionomycin induced intracellular Ca2 + mobilization. Cells were exposed to 100 pM PPADS (0) or vehicle (0) antagonist of P2X-purinoceptors (Lambrecht et al, 1992;Ziganshin et al, 1993) and of P2YI-purinoceptors (Brown et al, 1995). Its interaction with P2u-purinoceptors is less clear.…”

Section: Methodsmentioning

confidence: 99%

“…A 10 gM concentration of PPADS is sufficient to block most of the P2X and P2YI-purinoceptor-mediated responses (Lambrecht et al, 1992;Ziganshin et al, 1993;Brown et al, 1995 …”

Section: -E Ementioning

confidence: 99%

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The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization

Vigne¹,

Pacaud²,

Urbach³

et al. 1996

British J Pharmacology

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Section: Introductionmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…A 10 gM concentration of PPADS is sufficient to block most of the P2X and P2YI-purinoceptor-mediated responses (Lambrecht et al, 1992;Ziganshin et al, 1993;Brown et al, 1995 …”

Section: -E Ementioning

confidence: 99%

See 2 more Smart Citations

The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization

Vigne¹,

Pacaud²,

Urbach³

et al. 1996

British J Pharmacology

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“…The first identified P2X3 antagonists were negatively charged and/or high molecular weight arylpolysulfonate molecules [44], which showed to be unselective, as they were able to antagonize also the metabotropic P2Y receptors [45]. Further studies led to the discovery of a potent and selective P2X3 receptor antagonist, named A-317491 ( Fig.…”

Section: Introductionmentioning

confidence: 99%

2′,3′-O-Substituted ATP derivatives as potent antagonists of purinergic P2X3 receptors and potential analgesic agents

Ben

Marchenkova

Thomas

et al. 2016

Purinergic Signalling

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Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2′,3′-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized. These new compounds were functionally evaluated on native P2X3 receptors from mouse trigeminal ganglion (TG) sensory neurons using patch clamp recordings under voltage clamp configuration. Our data show that some of these molecules are potent (nanomolar range) and reversible inhibitors of P2X3 receptors, without any apparent effect on trigeminal GABA A and 5-HT 3 receptors, whose membrane currents were unaffected by the tested compounds.

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Synthesis and structure-activity relationships of pyridoxal-6-arylazo-5?-phosphate and phosphonate derivatives as P2 receptor antagonists

et al. 1998

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Novel analogs of the P2 receptor antagonist pyridoxal‐5′‐phosphate‐6‐phenylazo‐2′,4′‐disulfonate (PPADS) were synthesized. Modifications were made through functional group substitution on the sulfophenyl ring and at the phosphate moiety through the inclusion of phosphonates, demonstrating that a phosphate linkage is not required for P2 receptor antagonism. Substituted 6‐phenylazo and 6‐naphthylazo derivatives were also evaluated. Among the 6‐phenylazo derivatives, 5′‐methyl, ethyl, propyl, vinyl, and allyl phosphonates were included. The compounds were tested as antagonists at turkey erythrocyte and guinea‐pig taenia coli P2Y1 receptors, in guinea‐pig vas deferens and bladder P2X1 receptors, and in ion flux experiments by using recombinant rat P2X2 receptors expressed in Xenopus oocytes. Competitive binding assay at human P2X1 receptors in differentiated HL‐60 cell membranes was carried out by using [35S]ATP‐γ‐S. A 2′‐chloro‐5′‐sulfo analog of PPADS (C14H12O9N3ClPSNa), a vinyl phosphonate derivative (C15H12O11N3PS2Na3), and a naphthylazo derivative (C18H14O12N3PS2Na2), were particularly potent in binding to human P2X1 receptors. The potencies of phosphate derivatives at P2Y1 receptors were generally similar to PPADS itself, except for the p‐carboxyphenylazo phosphate derivative C15H13O8N3PNa and its m‐chloro analog C15H12O8N3ClPNa, which were selective for P2X vs. P2Y1 receptors. C15H12O8N3ClPNa was very potent at rat P2X2 receptors with an IC50 value of 0.82 μM. Among the phosphonate derivatives, [4‐formyl‐3‐hydroxy‐2‐methyl‐6‐(2‐chloro‐5‐sulfonylphenylazo)‐pyrid‐5‐yl]methylphosphonic acid (C14H12O8N3ClPSNa) showed high potency at P2Y1 receptors with an IC50 of 7.23 μM. The corresponding 2,5‐disulfonylphenyl derivative was nearly inactive at turkey erythrocyte P2Y1 receptors, whereas at recombinant P2X2 receptors had an IC50 value of 1.1 μM. An ethyl phosphonate derivative (C15H15O11N3PS2Na3), whereas inactive at turkey erythrocyte P2Y1 receptors, was particularly potent at recombinant P2X2 receptors. Drug Dev. Res. 45:52–66, 1998. Published 1998 Wiley‐Liss, Inc.

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PPADS: an antagonist at endothelial P_2Y‐purinoceptors but not P_2U‐purinoceptors

Abstract: provide a useful tool in the study of multiple subtypes of P2-purinoceptors. Furthermore the results are consistent with the hypothesis that ATP interacts with both receptor subtypes, but that the action of ADP is primarily at the P2Y-purinoceptor in these endothelial cells.

Cited by 64 publications

References 20 publications

The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization

The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization

2′,3′-O-Substituted ATP derivatives as potent antagonists of purinergic P2X3 receptors and potential analgesic agents

Synthesis and structure-activity relationships of pyridoxal-6-arylazo-5?-phosphate and phosphonate derivatives as P2 receptor antagonists

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PPADS: an antagonist at endothelial P2Y‐purinoceptors but not P2U‐purinoceptors

Abstract: provide a useful tool in the study of multiple subtypes of P2-purinoceptors. Furthermore the results are consistent with the hypothesis that ATP interacts with both receptor subtypes, but that the action of ADP is primarily at the P2Y-purinoceptor in these endothelial cells.

Cited by 64 publications

References 20 publications

The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization

The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization

2′,3′-O-Substituted ATP derivatives as potent antagonists of purinergic P2X3 receptors and potential analgesic agents

Synthesis and structure-activity relationships of pyridoxal-6-arylazo-5?-phosphate and phosphonate derivatives as P2 receptor antagonists

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PPADS: an antagonist at endothelial P_2Y‐purinoceptors but not P_2U‐purinoceptors