Highly Potent and Subtype Selective Ligands Derived byN-Methyl Scan of a Somatostatin Antagonist

2001 ◽  
Vol 44 (8) ◽  
pp. 1305-1311 ◽  
Author(s):  
W. G. Rajeswaran ◽  
Simon J. Hocart ◽  
William A. Murphy ◽  
John E. Taylor ◽  
David H. Coy
Keyword(s):  
Selective Ligands ◽  
Somatostatin Antagonist ◽  
Subtype Selective

Differential α2A- and α2C-adrenoceptor protein expression in presynaptic and postsynaptic density fractions of postmortem human prefrontal cortex

2018 ◽  
Vol 33 (2) ◽  
pp. 244-249 ◽  
Author(s):  
Amaia M Erdozain ◽  
Iria Brocos-Mosquera ◽  
Ane M Gabilondo ◽  
J Javier Meana ◽  
Luis F Callado
Keyword(s):  
Prefrontal Cortex ◽  
Protein Expression ◽  
Therapeutic Potential ◽  
Postsynaptic Density ◽  
Subcellular Fractionation ◽  
Similar Distribution ◽  
Density Fractions ◽  
Physiological Relevance ◽  
Selective Ligands ◽  
Subtype Selective

Background: Three different α2-adrenoceptor (α2-AR) subtypes have been described. The α2A-AR and α2C-AR subtypes are highly expressed in the human prefrontal cortex, where they modulate neurotransmission. However, due to the lack of subtype-selective ligands, the physiological relevance of both subtypes has not been fully resolved. Aims: In this context, the aim of the present study was to characterize the protein expression of both α2-AR subtypes, in different synaptic fractions of postmortem human prefrontal cortex. Methods: A subcellular fractionation of the samples was performed and the protein expression of α2A- and α2C-ARs was measured in presynaptic membranes and postsynaptic density fractions by Western blot. Results: The results revealed that the α2A-AR subtype is mainly located postsynaptically (95±3%) whereas the remaining 5±3% is in the presynapse. Conversely, the α2C-AR subtype showed a similar distribution between pre- and postsynaptic membranes, with a slightly higher percentage present in the presynapse (60±2% vs. 40±2%). Conclusions: These findings could explain some contradictory effects reported for α2-AR agonists and antagonists in the human prefrontal cortex. Furthermore, the present data could contribute to elucidating the therapeutic potential of selectively targeting α2A- or α2C-AR subtypes.

Synthesis and biological evaluation of novel cyclopropyl derivatives as subtype-selective ligands for estrogen receptor

2018 ◽  
Vol 70 (7) ◽  
pp. 910-918 ◽  
Author(s):  
Zunyuan Wang ◽  
Yewei Yang ◽  
Xiaoliang Zheng ◽  
Tao Zhang ◽  
Wenhai Huang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Biological Evaluation ◽  
Selective Ligands ◽  
Subtype Selective ◽  
Synthesis And Biological Evaluation

Serotonergic modulation of neuronal activity in rat midbrain periaqueductal gray

2013 ◽  
Vol 109 (11) ◽  
pp. 2712-2719 ◽  
Author(s):  
Hyo-Jin Jeong ◽  
Karen Lam ◽  
Vanessa A. Mitchell ◽  
Christopher W. Vaughan
Keyword(s):  
Brain Slices ◽  
Periaqueductal Gray ◽  
Membrane Excitability ◽  
Inhibitory Effects ◽  
Whole Cell Patch Clamp ◽  
Outward Currents ◽  
Selective Ligands ◽  
Inward Currents ◽  
Subtype Selective ◽  
Serotonergic Modulation

Serotonin (5-HT) modulates pain and anxiety from within the midbrain periaqueductal gray (PAG). In the present study, the effects of 5-HT- and 5-HT1/2 subtype-selective ligands on rat PAG neurons were examined using whole cell patch-clamp recordings in brain slices. In voltage clamp, 5-HT produced outward and inward currents in distinct subpopulations of neurons that varied throughout different subregions of the PAG. The 5-HT1A agonist R(+)-8-OH-DPAT (1 μM) produced outward currents in subpopulations of PAG neurons. By contrast, sumatriptan (1 μM) and other 5-HT1B, -D, and -F subtype agonists had little or no postsynaptic activity. The 5-HT2A/C agonists DOI (3 μM) and TCB-2 (1 μM) produced inward currents in subpopulations of PAG neurons, and DOI enhanced evoked inhibitory postsynaptic currents via a presynaptic mechanism. In current clamp, both R(+)-8-OH-DPAT and sumatriptan produced an excitatory increase in evoked mixed postsynaptic potentials (PSPs). In addition, R(+)-8-OH-DPAT, but not sumatriptan, directly hyperpolarized PAG neurons. By contrast, the 5-HT2 agonist DOI depolarized subpopulations of neurons and produced an inhibitory decrease in evoked mixed PSPs. These findings indicate that 5-HT1A and 5-HT1B/D ligands have partly overlapping inhibitory effects on membrane excitability and synaptic transmission within the PAG, which are functionally opposed by 5-HT2A/C actions in specific PAG subregions.

Mapping the Melatonin Receptor. 7. Subtype Selective Ligands Based on β-SubstitutedN-Acyl-5-methoxytryptamines and β-SubstitutedN-Acyl-5-methoxy-1-methyltryptamines

2006 ◽  
Vol 49 (12) ◽  
pp. 3509-3519 ◽  
Author(s):  
Andrew Tsotinis ◽  
Margarita Vlachou ◽  
Demetris P. Papahatjis ◽  
Theodora Calogeropoulou ◽  
Spyros P. Nikas ◽  
...  
Keyword(s):  
Melatonin Receptor ◽  
Selective Ligands ◽  
Subtype Selective

Identification of Endothelin Receptor Subtype (ETB) in Human Cerebral Cortex Using Subtype-Selective Ligands

2008 ◽  
Vol 62 (4) ◽  
pp. 1482-1488 ◽  
Author(s):  
Raquel Fernández-Durango ◽  
José A. Juan ◽  
Horatio Zimman ◽  
Francisco J. Moya ◽  
Mario Garcia de la Coba ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Receptor Subtype ◽  
Endothelin Receptor ◽  
Human Cerebral Cortex ◽  
Selective Ligands ◽  
Subtype Selective

Novel N-Substituted Indol-3-ylglyoxylamides Probing the LDiand L1/L2Lipophilic Regions of the Benzodiazepine Receptor Site in Search for Subtype-Selective Ligands†

2007 ◽  
Vol 50 (7) ◽  
pp. 1627-1634 ◽  
Author(s):  
Giampaolo Primofiore ◽  
Sabrina Taliani ◽  
Federico Da Settimo ◽  
Anna Maria Marini ◽  
Concettina La Motta ◽  
...  
Keyword(s):  
Receptor Site ◽  
Benzodiazepine Receptor ◽  
Selective Ligands ◽  
Subtype Selective

scholarly journals Norbenzomorphan Framework as a Novel Scaffold for Generating Sigma 2 Receptor/PGRMC1 Subtype-Selective Ligands

ChemMedChem ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. 556-561 ◽  
Author(s):  
James J. Sahn ◽  
Timothy R. Hodges ◽  
Jessica Z. Chan ◽  
Stephen F. Martin
Keyword(s):  
Selective Ligands ◽  
Subtype Selective ◽  
Novel Scaffold

Identification of Endothelin Receptor Subtypes in Rat Ciliary Body Using Subtype-Selective Ligands

1998 ◽  
Vol 66 (1) ◽  
pp. 69-79 ◽  
Author(s):  
AINHOA RIPODAS ◽  
JOSE A. DE JUAN ◽  
F.JOSE MOYA ◽  
ARTURO FERNANDEZ-CRUZ ◽  
RAQUEL FERNANDEZ-DURANGO
Keyword(s):  
Ciliary Body ◽  
Receptor Subtypes ◽  
Endothelin Receptor ◽  
Selective Ligands ◽  
Subtype Selective
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