Journal ArticleDOI
Heterologous supersensitization between serotonin2 and alpha2-adrenergic receptor-mediated intracellular calcium mobilization in human platelets
Ariyuki Kagaya,Masahiko Mikuni,Hideko Yamamoto,S. Muraoka,Shigeto Yamawaki,Kiyohisa Takahashi +5 more
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TLDR
The results suggest that the supersensitization was caused from intracellular Ca2+ storage sites through a G protein-coupled pathway.Abstract:
Recent reports suggest that serotonin (5-HT)2 receptor-mediated second messenger systems are enhanced in platelets of affective disorders. To make the mechanism of the enhanced response clear, we investigated 5-HT2 and alpha (α)2-adrenergic receptor-induced intracellular calcium (Ca2+) mobilization in platelets of healthy volunteers, using fura-2. 5-HT2 and α2-adrenergic receptor-mediated Ca2+ mobilization was enhanced by prior exposure to the other type of agonist, so called “heterologous supersensitization”. The supersensitization was due to the enhancement of maximal response without change in agonist affinity. Chelating extracellular Ca2+ did not diminish the supersensitization. This enhancement of Ca2+ mobilization was not inhibited by H-7, an inhibitor of protein kinase C. However, this supersensitization was inhibited by pretreatment with sodium fluoride which directly activates guanine nucleotide binding regulatory proteins (G proteins). These results suggest that the supersensitization was caused from intracellular Ca2+ storage sites through a G protein-coupled pathway.read more
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The Second Intracellular Loop of the α2-Adrenergic Receptors Determines Subtype-specific Coupling to cAMP Production
TL;DR: Site-directed mutagenesis of non-conserved amino acids in the second intracellular loop of the α2A subtype indicated that several residues are involved in the coupling specificity, and biphasic dose-response curve could be seen, suggesting that this loop is important for determining the subtype-specific coupling of α2-ARs to cAMP production.
Patent
1, 4-disubstituted 3-cyano-pyridone derivatives and their use as positive allosteric modulators of MGLUR2-receptors
Hassan Julien Imogai,José Maria Cid-Núñez,Jose Ignacio Andres-Gil,Andrés Avelino Trabanco-Suárez,Julen Oyarzabal Santamarina,Frank Matthias Dautzenberg,Gregor James Macdonald,Shriley Elizabeth Pullan,Robert Johannes Lütjens,Guillaume Albert Jacques Duvey,Vanthea Nhem,Terry Patrick Finn,Gagik Melikyan +12 more
TL;DR: Pyridinone as mentioned in this paper is a positive allosteric modulator of metabotropic receptors -sub-type 2 ("mGluR2") which is useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction.
Journal Article
Enhanced calcium response to serotonin in platelets from patients with affective disorders.
TL;DR: An enhanced intracellular Ca2+ rise in response to 5-HT in platelets from both bipolar patients and patients with major depression is found.
Patent
Imidazo[1,2-A]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors
TL;DR: In this article, a positive allosteric modulator of metabotropic receptors-subtype 2 ('mGluR2') which is useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGlu receptor is involved.
Patent
1,2,4-Triazolo [4,3-A] Pyridine Derivatives and Their Use For The Treatment of Prevention of Neurological and Psychiatric Disorders
Cid-Nunez Jose Maria,Daniel Oehlrich,Andrés Avelino Trabanco-Suárez,Gary Tresadern,Vega Ramiro Juan Antonio,Macdonald Gregor James +5 more
TL;DR: In this paper, a triazolo[4,3-a]pyridine derivatives of Formula (I) were described, where all radicals are defined as defined in the claims.
References
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