Book Chapter10.1007/978-1-4615-2011-5_18
Novel ATP Agonists Reveal Receptor Heterogeneity Within P2X and P2Y Subtypes
Kenneth A. Jacobson,Bilha Fischer,Michel Maillard,José L. Boyer,Charles H.V. Hoyle,T. Kendall Harden,Geoffrey Burnstock +6 more
- 01 Jan 1995
- pp 149-156
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TL;DR: It is the goal to establish systematically the structure-activity relationships for newly synthesized derivatives in much the same fashion as has been used for adenosine receptors to establish systematic relationships for P2 receptor agonists.
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Abstract: The selection of analogues of adenosine 5’-triphosphate (ATP) useful as P2 receptor agonists is limited in number [1] relative to most other cell membrance receptors. It is our goal to establish systematically the structure-activity relationships for newly synthesized derivatives in much the same fashion as has been used for adenosine receptors [2]. Impeding this development is the current lack of high-affinity radioligands for general applicability to P2 receptor subtypes. For example, [35S]β-thio-ADP, which was shown to bind specifically to P2Y receptors in turkey erythrocyte membrances [3], binds to a site in bovine brain membranes that does not resemble P2Y receptors in rank order of ligand potencies [4]. Another factor that contributes to the lack of progress in the development of P2 ligands is the incomplete knowledge of subtype classification [5,19]. The latter difficulty will be alleviated as the cloning of P2 receptors progresses [6–8].
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The birth and postnatal development of purinergic signalling
TL;DR: A detailed account of the early developments and current status of purinergic signalling is presented and the current knowledge on purinoceptors, their distribution and role in signal transduction in various tissues in physiological and pathophysiological conditions is summarized.
146
Extracellular adenosine-induced apoptosis in mouse neuroblastoma cells: studies on involvement of adenosine receptors and adenosine uptake.
S. Mariette Schrier,Erica W. van Tilburg,Hans van der Meulen,Ad P. IJzerman,Gerald J Mulder,J. Fred Nagelkerke +5 more
TL;DR: The results indicate that adenosine receptors are not involved in adenosinesine-induced apoptosis in N1E-115 cells, but that uptake of adenoine and its subsequent phosphorylation is required.
65
Discovery and Biological Evaluation of Novel Cyanoguanidine P2X7 Antagonists with Analgesic Activity in a Rat Model of Neuropathic Pain
Arturo Perez-Medrano,Diana L. Donnelly-Roberts,Prisca Honore,Gin C. Hsieh,Marian T. Namovic,Sridhar Peddi,Qi Shuai,Ying Wang,Connie R. Faltynek,Michael F. Jarvis,William A. Carroll +10 more
TL;DR: A novel series of cyanoguanidines that are potent and selective P2X(7) receptor antagonists against the other P2 receptor subtypes and effectively reduced nociception in a rat model of neuropathic pain (Chung model).
47
Challenges in developing P2 purinoceptor-based therapeutics.
Michael Williams
- 28 Sep 2007
TL;DR: The key to exploiting the P2 purinoceptor area to enhance understanding of disease aetiology and concurrent therapeutic potential will be to focus efforts on the identification of novel pharmacophores that have potent and selective interactions with the various receptor subtypes as potential new leads.
22
Structure Activity Relationships of P2 Receptor Agonists and Antagonists
Kenneth A. Jacobson,Yong-Chul Kim,Emidio Camaioni,A. Michiel van Rhee +3 more
- 01 Jan 1998
TL;DR: The recently reorganized nomenclature of P2 receptors divides them into ligand-gated ion channels and metabotropic G protein-coupled subtypes (P2Y and P2X), and the most potent native nucleotide is adenosine triphos-phate (ATP).
17
References
Is there a basis for distinguishing two types of P2-purinoceptor?
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Purinoceptors: Are there families of P2X and P2Y purinoceptors?
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Adenosine Receptors: Pharmacology, Structure–Activity Relationships, and Therapeutic Potential
TL;DR: Adenosine agonists and antagonists have entered clinical trials and none of these, to the authors’ knowledge, have been successful, and advances in knowledge related to adenosine function at the molecular level will be reviewed together with information on the structure–activity relationships for a number of pharmacophore series interacting with adenosines receptors.
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Phosphoinositide hydrolysis by guanosine 5'-[gamma-thio]triphosphate-activated phospholipase C of turkey erythrocyte membranes.
TL;DR: The effects of ATP on inositol phosphate formation apparently involve the contributions of two phenomena, the P2-receptor agonist 2-methylthioadenosine triphosphate (2MeSATP) and higher concentrations of ATP, apparently by supporting the synthesis of substrate phospholipids.
Guanine Nucleotide-sensitive Interaction of a Radiolabeled Agonist with a Phospholipase C-linked P2y-purinergic Receptor
TL;DR: The data are consistent with the idea that [35S]ADP beta S may be used to radiolabel the P2y-purinergic receptor linked to activation of phospholipase C in turkey erythrocyte membranes.
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