The Experts below are selected from a list of 153 Experts worldwide ranked by ideXlab platform
James T. Slama - One of the best experts on this subject based on the ideXlab platform.
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Nicotinic Acid Adenine Dinucleotide Phosphate Analogues Substituted on the Nicotinic Acid and Adenine Ribosides. Effects on ReceptorMediated Ca2+ Release
Journal of Medicinal Chemistry, 2015Co-Authors: Christopher J. Trabbic, Timothy F Walseth, Fan Zhang, James T. SlamaAbstract:Nicotinic Acid adenine dinucleotide phosphate (NAADP) is a Ca2+ releasing intracellular second messenger in both mammals and echinoderms. We report that large functionalized substituents introduced at the Nicotinic Acid 5-position are recognized by the sea urchin receptor, albeit with a 20–500-fold loss in agonist potency. 5-(3-Azidopropyl)-NAADP was shown to release Ca2+ with an EC50 of 31 μM and to compete with NAADP for receptor binding with an IC50 of 56 nM. Attachment of charged groups to the Nicotinic Acid of NAADP is associated with loss of activity, suggesting that the nicotinate riboside moiety is recognized as a neutral zwitterion. Substituents (Br– and N3−) can be introduced at the 8-adenosyl position of NAADP while preserving high potency and agonist efficacy and an NAADP derivative substituted at both the 5-position of the Nicotinic Acid and at the 8-adenosyl position was also recognized although the agonist potency was significantly reduced.
Christopher J. Trabbic - One of the best experts on this subject based on the ideXlab platform.
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Nicotinic Acid Adenine Dinucleotide Phosphate Analogues Substituted on the Nicotinic Acid and Adenine Ribosides. Effects on ReceptorMediated Ca2+ Release
Journal of Medicinal Chemistry, 2015Co-Authors: Christopher J. Trabbic, Timothy F Walseth, Fan Zhang, James T. SlamaAbstract:Nicotinic Acid adenine dinucleotide phosphate (NAADP) is a Ca2+ releasing intracellular second messenger in both mammals and echinoderms. We report that large functionalized substituents introduced at the Nicotinic Acid 5-position are recognized by the sea urchin receptor, albeit with a 20–500-fold loss in agonist potency. 5-(3-Azidopropyl)-NAADP was shown to release Ca2+ with an EC50 of 31 μM and to compete with NAADP for receptor binding with an IC50 of 56 nM. Attachment of charged groups to the Nicotinic Acid of NAADP is associated with loss of activity, suggesting that the nicotinate riboside moiety is recognized as a neutral zwitterion. Substituents (Br– and N3−) can be introduced at the 8-adenosyl position of NAADP while preserving high potency and agonist efficacy and an NAADP derivative substituted at both the 5-position of the Nicotinic Acid and at the 8-adenosyl position was also recognized although the agonist potency was significantly reduced.
Andrew Green - One of the best experts on this subject based on the ideXlab platform.
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molecular identification of high and low affinity receptors for Nicotinic Acid
Journal of Biological Chemistry, 2003Co-Authors: Alan Wise, Steven M Foord, Neil J Fraser, Ashley A Barnes, Nabil Elshourbagy, Michelle M Eilert, Diane M Ignar, Paul R Murdock, Klaudia Steplewski, Andrew GreenAbstract:Nicotinic Acid has been used clinically for over 40 years in the treatment of dyslipidemia producing a desirable normalization of a range of cardiovascular risk factors, including a marked elevation of high density lipoprotein and a reduction in mortality. The precise mechanism of action of Nicotinic Acid is unknown, although it is believed that activation of a Gi-G protein-coupled receptor may contribute. Utilizing available information on the tissue distribution of Nicotinic Acid receptors, we identified candidate orphan receptors. The selected orphan receptors were screened for responses to Nicotinic Acid, in an assay for activation of Gi-G proteins. Here we describe the identification of the G protein-coupled receptor HM74 as a low affinity receptor for Nicotinic Acid. We then describe the subsequent identification of HM74A in follow-up bioinformatics searches and demonstrate that it acts as a high affinity receptor for Nicotinic Acid and other compounds with related pharmacology. The discovery of HM74A as a molecular target for Nicotinic Acid may facilitate the discovery of superior drug molecules to treat dyslipidemia.
Kiyoshi Furuichi - One of the best experts on this subject based on the ideXlab platform.
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molecular identification of Nicotinic Acid receptor
Biochemical and Biophysical Research Communications, 2003Co-Authors: Takatoshi Soga, Masazumi Kamohara, Jun Takasaki, Shunichiro Matsumoto, Tetsu Saito, Takahide Ohishi, Hideki Hiyama, Ayako Matsuo, Hitoshi Matsushime, Kiyoshi FuruichiAbstract:Nicotinic Acid and its derivative, Acipimox, have been widely used in the treatment of hyperlipidemia. Pharmacological studies have demonstrated that they exert the beneficial effect through the activation of a Gi-protein-coupled receptor on adipocyte, which has remained elusive to date. Here we show that a novel GPCR, designated HM74b because of its high similarity to HM74, is a receptor for Nicotinic Acid. HM74b mRNA is found in human, murine, and rat adipose tissues. Nicotinic Acid and Acipimox inhibit forskolin-stimulated intracellular cAMP accumulation in human HM74b-expressing cells and activate GTP gamma S binding in a dose-dependent manner. [3H]Nicotinic Acid specifically binds to HM74b-expressing membrane and its binding is replaced by Acipimox. This finding will open a new phase of research on the physiological role of Nicotinic Acid and will be a clue to develop novel antihyperlipidemic drugs.
Timothy F Walseth - One of the best experts on this subject based on the ideXlab platform.
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Nicotinic Acid Adenine Dinucleotide Phosphate Analogues Substituted on the Nicotinic Acid and Adenine Ribosides. Effects on ReceptorMediated Ca2+ Release
Journal of Medicinal Chemistry, 2015Co-Authors: Christopher J. Trabbic, Timothy F Walseth, Fan Zhang, James T. SlamaAbstract:Nicotinic Acid adenine dinucleotide phosphate (NAADP) is a Ca2+ releasing intracellular second messenger in both mammals and echinoderms. We report that large functionalized substituents introduced at the Nicotinic Acid 5-position are recognized by the sea urchin receptor, albeit with a 20–500-fold loss in agonist potency. 5-(3-Azidopropyl)-NAADP was shown to release Ca2+ with an EC50 of 31 μM and to compete with NAADP for receptor binding with an IC50 of 56 nM. Attachment of charged groups to the Nicotinic Acid of NAADP is associated with loss of activity, suggesting that the nicotinate riboside moiety is recognized as a neutral zwitterion. Substituents (Br– and N3−) can be introduced at the 8-adenosyl position of NAADP while preserving high potency and agonist efficacy and an NAADP derivative substituted at both the 5-position of the Nicotinic Acid and at the 8-adenosyl position was also recognized although the agonist potency was significantly reduced.
