Translational research of bombesin-like peptides in lung cancer
Bombesin (BB)-like peptides function as autocrine growth factors in the neuroendocrine tumor small cell lung cancer (SCLC). Gastrin releasing peptide (GRP) is secreted from SCLC cells when the cAMP is elevated by addition of secretin to SCLC cells (Moody et al., Science 1981; 214: 1246). GRP binds to BB2 receptors (R), causing phosphatidylinositol (PI) turnover and SCLC proliferation. The monoclonal antibody 2A11 neutralizes GRP inhibiting SCLC proliferation in vitro and in vivo (Cuttitta et al.,Nature 1985; 316: 823). (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Terry Moody, Marcello Leopoldo, Robert Jensen Source Type: research
VGF and its C-terminal peptide TLQP-62 regulate memory formation and depressive behavior via a BDNF-TrkB-dependent mechanism
Regulated expression and secretion of brain-derived neurotrophic factor (BDNF), which activates TrkB receptor signaling, is thought to play a critical role in cognition, depressive behavior, and antidepressant efficacy. Our lab has sought to identify additional modulators of cognitive and depressive behavior that regulate activity-dependent BDNF secretion and/or potentiate TrkB receptor signaling. In the adult hippocampus, expression of the granin family protein VGF and secretion of its C-terminal peptide TLQP-62 are required for fear memory formation and the response to antidepressants, including voluntary exercise, imipr...
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Wei-Jye Lin, Cheng Jiang, Masato Sadahiro, Ozlem Bozdagi, Lucy Vulchanova, Scott Russo, Cristina Alberini, Stephen Salton Source Type: research
Influence of Chronic Variable Stress in Neurotoxin and Genetic Models of Parkinson's Disease
The contribution of stress or stress-induced depression to the neuropathology of Parkinson ’s disease (PD) and exacerbation of parkinsonian symptoms is receiving more attention of late. We have recently demonstrated that exposure to a chronic variable stress (CVS) regimen markedly increased degeneration of nigral dopaminergic neurons and worsened behavioral dysfunction in the 6-OHDA rat model of PD. Regarding potential mechanisms, worsening of behavioral outcome and neurodegeneration was not induced by glucocorticoids alone, suggesting the involvement of other stress-induced processes. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Kim Seroogy, Tara Kyser, Kerstin Lundgren, Ann Hemmerle Source Type: research
What is the relevance of vascular responses to CGRP?
TRPA1-expressing sensory nerves contain and release the highly potent vasodilator α-calcitonin gene-related peptide (α-CGRP)1. We demonstrated that TRPA1 acts as a primary vascular cold sensor2. The initial cold-induced vasoconstriction is mediated via TRPA1-dependent superoxide production, stimulating α2c-adrenoceptors and rho-kinase mediated myosin-light-chain phosphorylatio n. The subsequent restorative blood flow is dependent on TRPA1 activation, mediated by CGRP and nitric-oxide. The TRPA1-CGRP dilator pathway is thus important in the physiological reflex to local cold response. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Aisah Aubdool, Susan Brain Source Type: research
H2S-NO-TRPA1-CGRP signalling controls meningeal blood flow
Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) released in the dura mater encephali mediate meningeal blood flow elevation possibly linked to the pathopysiology of headaches. Thereby nitroxyl (HNO) generated by the reaction of NO with hydrogen sulfide (H2S) may be a major vasodilatory agent. We investigated the involvement of HNO in meningeal blood flow regulation and CGRP release in models of meningeal nociception. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Maria Dux, Christine Will, Birgit Vogler, Milos R. Filipovic, Karl Messlinger Source Type: research
Role and activation mechanism of the Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel in mouse models of chronic pain
Few contradictory data are available about the activation and pathophysiological relevance of Transient Receptor Potential Ankyrin 1 (TRPA1) in chronic inflammation and pain. Noxious mediators produced by the semicarbazide-sensitive amine-oxydase (SSAO) during tissue injury, such as formaldehyde and methylglyoxal, are its stimulators, but link between TRPA1 and SSAO products, and analgesic effect of SSAO inhibitors have not been investigated. We studied the role of TRPA1, SSAO, and their interactions in chronic pain models. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Zsuzsanna Helyes, Balint Scheich, Adam Horvath, Balint Botz, Valeria Tekus, Andrea Czompa, Robert Ludmerczki, Erika Pinter, Janka Csepregi, Janos Szolcsanyi, Attila Mocsai, Peter Matyus Source Type: research
TRPA1 receptor-mediated effects of H2S donors and polysulfides
We presented earlier that they increase intracellular Ca2+ concentration ([Ca2+]i) in trigeminal ganglion (TRG) cells by TPPA1 dependent manner. Proinflammatory (e.g. SP, CGRP), as well as anti-inflammatory neuropeptides (e.g. somatostatin) are released from the activated nerve endings and influence pain sensation and inflammatory processes. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Erika Pinter, Gabor Pozsgai, Zsofia Hajna, Eva Saghy, Adam Horvath, Eva Szoke, Cecilia Sar, Ter éz Bagoly, Aisah Aubdool, Susan Brain, Zsuzsanna Helyes Tags: S2/4 Source Type: research
Biased Agonism at Cannabinoid CB1 and δ-Opioid Receptors; Therapeutic Potential
Cannabinoid CB1 (CB1R) and δ-opioid receptors (DOR) couple to a similar range of signal transduction systems and have similar physiological functions. Here we have characterised the signalling profiles of a number of standard and novel agonists at each of the receptors. Inhibition of forskolin-stimulated cyclic AMP accumulat ion, Erk42/44 MAP kinase phosphorylation and β2-arrestin recruitment were measured in CHO and HEK cells over-expressing human CB1R and DOR. Most CB1 agonists were biased (i.e. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: David Kendall, Stephen Alexander, Richard Priestley, Muhammad Asghar, Bengt von Mentzer Source Type: research
Effect of PN6047 on chronic pain, in vivo, PK-ADME, safety pharmacology and toxicology
PN6047 is a novel compound designed for treatment of chronic pain. The compound is a biased selective delta opioid receptor agonist. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Bengt von Mentzer, Urban Fagerholm, Zsuzsanna Helyes, David Kendall Source Type: research
Control of the sympathetic nervous system by TRPV1 in the regulation of body temperature
Transient receptor potential vanilloid 1 (TRPV1) is involved in pain and neurogenic inflammation. It has recently been found that TRPV1 anatgonism causes hyperthermia in multiple species from mice to humans. In the present study, we investigated whether TRPV1 regulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radio-telemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected via the peritoneal route. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Khadija Alawi, Aisah Aubdool, Lihuan Liang, Elena Wilde, Abhinav Vepa, Paraskevi-Maria Psefteli, Susan Brain, Julie Keeble Source Type: research
Transport of TRPV1 ligands through the blood-brain barrier
This study aimed to determine whether TRPV1 ligands are substrates for the P-gp transporter. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Luke McNickle, Rachel Brown, Julie Keeble, Gayathri Sekhar, Sarah Thomas Source Type: research
Evidence for the role of sphingomyelin and lipid rafts in Ca2+-gating of the Transient Receptor Potential channels in trigeminal sensory neurons and peripheral nerve terminals
Transient Receptor Potential (TRP) cation as the TRP Vanilloid 1 and TRP Ankyrin repeat domain 1 channels (TRPV1 and TRPA1) are nocisensors playing important role to trigger pain. Two “melastatin” TRP receptors as TRPM8 and TRPM3 are also expressed in subgroups of primary sensory neurons. All these cation channels serve as thermosensors and are suitable to be activated also by several exogenous and endogenous chemical ligands. The role of plasma membrane microdomains of lipid rafts was analysed on isolated trigeminal (TG) neurons and TRPV1-expressing CHO cells by measuring agonists-induced Ca2+ transients with ratiomet...
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Éva Szoke, Éva Sághy, Maja Payrits, Zsuzsanna Helyes, János Erostyák, Tibor Jánosi, György Sétáló Tags: S4/3 Source Type: research
Genetic deletion of the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor inhibits cuprizon-induced demyelination in mice
Multiple sclerosis (MS) is a neurodegenerative disease with inflammation and demyelination. Administration of cuprizone to mice induces primary oligodendroglial apoptosis, secondary demyelination with macrophage invasion and astrocytosis particularly in the corpus callosum. Since the presence of functional TRPA1 receptors has been detected in astrocytes, we investigated the role of this receptor in a cuprizone-induced experimental demyelination model. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Eva Saghy, Kata Bolcskei, Acs Peter, Komoly Samuel, Aniko Perkecz, Balazs Gaszner, Eva Sipos, Eva Szoke, Agnes Kemeny, Sandor Zoltan, Zsuzsanna Helyes, Erika Pinter Source Type: research
CGRP in the 21st century: A well-aged and blended peptide
This session will address the emerging role of CGRP as a therapeutic target for several common and debilitating disorders. The neuropeptide CGRP is increasingly recognized as a key player in several disease states. CGRP is ideally cast for this role since it lies at the intersection of both peripheral inflammation and central modulation mechanisms. An introductory overview will first describe the peripheral and central actions of CGRP. The speakers will then provide an update on CGRP actions in the trigeminovascular system in the context of the exciting success of CGRP-blocking antibodies in clinical trials for preventing ...
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Andrew Russo Source Type: research
Sites of CGRP release and actions in the trigeminovascular system
Attacks of primary headaches are accompanied by the release of the potent vasodilator calcitonin gene-related peptide (CGRP) from activated meningeal afferents which may increase intracranial blood flow. We aimed to localize the sites of CGRP release in an in vivo rodent preparation and to record simultaneously meningeal and medullary blood flow. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Karl Messlinger, Christine Will, Michael Fischer, M ária Dux Source Type: research
