Structure–activity relationships of novel P2-receptor antagonists structurally related to Reactive Blue 2

Glänzel, Markus; Bültmann, Ralph; Starke, Klaus; Frahm, A. W.

doi:10.1016/j.ejmech.2005.07.007

Cited by 41 publications

(38 citation statements)

References 41 publications

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“…The molecular structure of RB-2 contains three sulfonic acid residues. RB-2 is defined as a mixture of two constitutional isomers with a sulfonic acid residue in the meta-and para-position at ring F, respectively (CAS number 12236-82-7; see also Glä nzel et al, 2003Glä nzel et al, , 2005. The data of our present study indicate that the sulfonic acid residue at ring D of antagonists based on the structure of RB-2 ( Fig.…”

supporting

confidence: 49%

“…The following drugs were used: adenosine 5Ј-diphosphate sodium salt (ADP), adenosine 5Ј-triphosphate sodium salt (ATP), forskolin, 2-methylthioadenosine 5Ј-diphosphate trisodium salt (2-methylthio-ADP, 2-MeSADP), reactive red 2 and uridine 5Ј-diphosphate-glucose (UDP-glucose; Sigma Chemie, Deisenhofen, Germany); 3Ј-O-(4-benzoyl)benzoyl-ATP sodium (Invitrogen); RB-2 (mixture of reactive blue 2 meta and reactive blue 2 para; Ega Chemie, Mannheim, Germany); cibacron blue 3GA, MG 38-1 (for structure see Glä nzel et al, 2003Glä nzel et al, , 2005, reactive blue 2 meta, and reactive blue 2 para (synthesized by Markus Glä nzel, Department of Pharmacology and Toxicology, University of Freiburg; for structures see Glä nzel et al, 2003Glä nzel et al, , 2005; PSB-0739 (see Fig. 1), PSB-0801 (see Fig.…”

Section: Methodsmentioning

confidence: 99%

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Interaction of New, Very Potent Non-Nucleotide Antagonists with Arg256 of the Human Platelet P2Y₁₂ Receptor

Hoffmann¹,

Baqi²,

Morena³

et al. 2009

J Pharmacol Exp Ther

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The P2Y 12 receptor plays a crucial role in platelet aggregation. In the present study, we analyzed the properties of non-nucleotide antagonists at the recombinant human P2Y 12 receptor and searched for amino acids involved in the molecular interaction. Receptor function was assessed by measuring the cAMP response element (CRE)-directed luciferase expression in Chinese hamster ovary cells. The cellular cAMP production was accelerated by forskolin; 2-methylthio-ADP was used to activate the wild-type P2Y 12 receptor or mutant constructs. 2-Methylthio-ADP inhibited the CRE-dependent luciferase expression with an IC 50 value of approximately 1 nM. The anthraquinone derivative reactive blue 2 used at increasing concentrations shifted the concentration-response curve of 2-methylthio-ADP to the right in a manner compatible with competitive antagonism (pA 2 value, 7.4). Its analog, 1-amino-4-[4-phenylamino-3-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (PSB-0739), showed a markedly higher antagonistic potency with a pA 2 value of 9.8. In cells expressing the R256A-mutant receptor, the potencies of both reactive blue 2 (apparent pK B , 5.9) and PSB-0739 (apparent pK B , 9.1) were decreased. The same was true for the pure reactive blue 2 meta-and para-isomers and for the ortho-isomer cibacron blue 3GA. In contrast, the analog, 1-amino-4-[4-anilino-phenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, lacking a sulfonic acid residue at ring D (PSB-0826), showed similar pK B values at wild-type (8.4) and R256A-mutant receptors (8.3). In summary, the results demonstrate that PSB-0739 is the most potent competitive nonnucleotide antagonist at the human P2Y 12 receptor described so far. The results also indicate that the sulfonic acid residue at ring D is involved in the interaction of antagonists derived from reactive blue 2 with the residue Arg256 of the human P2Y 12 receptor.

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supporting

confidence: 49%

Section: Methodsmentioning

confidence: 99%

Interaction of New, Very Potent Non-Nucleotide Antagonists with Arg256 of the Human Platelet P2Y₁₂ Receptor

Hoffmann¹,

Baqi²,

Morena³

et al. 2009

J Pharmacol Exp Ther

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“…Furthermore, it does not discriminate between native P2X 1 receptors of the rat vas deferens and P2Y 1 -like receptors of the guinea-pig taenia coli (Glanzel et al, 2003). Moreover, it has been reported that commercially available RB-2 has antagonistic activities at rat P2X 1 , P2X 2 , P2Y 1 , P2Y 4 , and P2Y 6 (Glanzel et al, 2003(Glanzel et al, , 2005Ralevic and Burnstock, 1998), whereas P2X 3 , P2X 5 , P2X 6 , P2X 7 , and P2Y 11 were not been examined as yet (Ralevic and Burnstock, 1998). Therefore, RB-2 is not speciWc to rat P2Y 4 .…”

Section: Evects Of Antagonists and Agonists At Rp2y 4 On Native Striamentioning

confidence: 97%

Reactive blue 2, an antagonist of rat P2Y4, increases K+ secretion in rat cochlea strial marginal cells

et al. 2006

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“…[8][9][10] The phasic contractile response is abolished by P2X1-purinoceptor antagonist a,b-methylene (m) ATP (desensitization) 11,12 and tonic contraction is depressed by a 1 -adrenoceptor antagonist prazosin. 13 Recently, it is also reported that human vas deferens has both P2X1-purinoceptor and a 1 -adrenoceptor, the former being antagonized by a,b-mATP and the latter by prazosin.…”

Section: Introductionmentioning

confidence: 99%

T‐ and L‐type calcium channels mediate α₁‐adrenoceptor‐evoked contraction in the guinea‐pig vas deferens

Shishido

Sakai

Tosaka

2009

Neurourology and Urodynamics

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The results may indicate that the alpha(1)-adrenoceptor-induced contraction was mediated by Ca(2+) influx through T- and L-type Ca(2+) channels for the early and late alpha(1)-components, respectively and that SK and BK channels contributed to protect the musculature of the guinea-pig vas deferens from excess tension development induced by sympathetic volley. Neurourol. Urodynam. 28:447-454, 2009. (c) 2009 Wiley-Liss, Inc.

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Structure–activity relationships of novel P2-receptor antagonists structurally related to Reactive Blue 2

Cited by 41 publications

References 41 publications

Interaction of New, Very Potent Non-Nucleotide Antagonists with Arg256 of the Human Platelet P2Y₁₂ Receptor

Interaction of New, Very Potent Non-Nucleotide Antagonists with Arg256 of the Human Platelet P2Y₁₂ Receptor

Reactive blue 2, an antagonist of rat P2Y4, increases K+ secretion in rat cochlea strial marginal cells

T‐ and L‐type calcium channels mediate α₁‐adrenoceptor‐evoked contraction in the guinea‐pig vas deferens

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Structure–activity relationships of novel P2-receptor antagonists structurally related to Reactive Blue 2

Cited by 41 publications

References 41 publications

Interaction of New, Very Potent Non-Nucleotide Antagonists with Arg256 of the Human Platelet P2Y12 Receptor

Interaction of New, Very Potent Non-Nucleotide Antagonists with Arg256 of the Human Platelet P2Y12 Receptor

Reactive blue 2, an antagonist of rat P2Y4, increases K+ secretion in rat cochlea strial marginal cells

T‐ and L‐type calcium channels mediate α1‐adrenoceptor‐evoked contraction in the guinea‐pig vas deferens

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Interaction of New, Very Potent Non-Nucleotide Antagonists with Arg256 of the Human Platelet P2Y₁₂ Receptor

Interaction of New, Very Potent Non-Nucleotide Antagonists with Arg256 of the Human Platelet P2Y₁₂ Receptor

T‐ and L‐type calcium channels mediate α₁‐adrenoceptor‐evoked contraction in the guinea‐pig vas deferens