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Dora Reglodi, Adel Jungling, Rémi Longuespée, Joerg Kriegsmann, Rita Casadonte, Mark Kriegsmann, Tamas Juhasz, Sebastian Bardosi, Andrea Tamas, Balazs Daniel Fulop, Krisztina Kovacs, Zsuzsanna Nagy, Jason Sparks, Attila Miseta, Gabriel Mazzucchelli, Hitoshi Hashimoto, Attila Bardosi
Dysregulation of neuropeptides may play an important role in aging-induced impairments. Among them, pituitary adenylate cyclase activating polypeptide (PACAP) is a potent cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. We hypothesized that the progressive decline of PACAP throughout life, and the well-known general cytoprotective effects of PACAP lead to age-related pathophysiological changes in PACAP deficiency, supported by the increased vulnerability to various stressors of animals partially or totally lacking PACAP...
May 17, 2018: Journal of Pathology
Michael G Moldavan, Patricia J Sollars, Michael R Lasarev, Charles N Allen, Gary E Pickard
Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator that functions as a biological clock. ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. Pituitary adenylate cyclase-activating polypeptide (PACAP) is also packaged into vesicles in ipRGCs and PACAP may be coreleased with glutamate in the SCN...
May 2018: ENeuro
Javad Mahmoudi, Gisou Mohaddes, Marjan Erfani, Saeed Sadigh-Eteghad, Pouran Karimi, Mojgan Rajabi, Siamak Reyhani-Rad, Fereshteh Farajdokht
Chronic migraine dramatically affects the quality of life in the migraineurs. This study examined the effect of chronic cerebrolysin (CBL) treatment on the migraine-associated symptoms in a rat model of migraine. Experiments were carried out on 8 weeks, male Wistar rats. Chronic migraine was modeled by injection (10 mg/kg, i.p) of nitroglycerin (NTG) on days 3, 5, 7, and 9. CBL (2.5 and 5 ml/kg, i.p.) was injected every day for 10 days. Mechanical and thermal withdrawal thresholds of the hind paw were examined by von Frey hairs and hot plate, respectively...
May 9, 2018: Brain Research Bulletin
Messoud Ashina, Paolo Martelletti
No abstract text is available yet for this article.
May 8, 2018: Journal of Headache and Pain
Yusuke Shintani, Atsuko Hayata-Takano, Keita Moriguchi, Takanobu Nakazawa, Yukio Ago, Atsushi Kasai, Kaoru Seiriki, Norihito Shintani, Hitoshi Hashimoto
A pituitary adenylate cyclase-activating polypeptide (PACAP)-specific receptor, PAC1R, is coupled with multiple signal transduction pathways including stimulation of adenylate cyclase, phospholipase C and extracellular-signal regulated kinase (ERK)1/2. PAC1R has been shown to exert its long-lasting and potent signals via β-arrestin1 and β-arrestin2. However, the precise roles of the two β-arrestin isoforms in PACAP-PAC1R signaling remain unclear. Here we examined the interaction between the two β-arrestin isoforms and PAC1R, β-arrestin-dependent PAC1R subcellular localization and ERK1/2 activation...
2018: PloS One
Jae Eun Choi, Anna Di Nardo
The epidermis closely interacts with nerve endings, and both epidermis and nerves produce substances for mutual sustenance. Neuropeptides, like substance P (SP) and calcitonin gene-related protein (CGRP), are produced by sensory nerves in the dermis; they induce mast cells to release vasoactive amines that facilitate infiltration of neutrophils and T cells. Some receptors are more important than others in the generation of itch. The Mas-related G protein-coupled receptors (Mrgpr) family as well as transient receptor potential ankyrin 1 (TRPA1) and protease activated receptor 2(Par2) have important roles in itch and inflammation...
April 30, 2018: Seminars in Immunopathology
Mathilde Poujol de Molliens, Myriam Létourneau, Dominic Devost, Terence E Hébert, Alain Fournier, David Chatenet
The pituitary adenylate cyclase-activating polypeptide (PACAP), which exists in two isoforms of 27 and 38 amino acids, can induce neuronal protection in vitro and in vivo following the activation of PAC1, a class B G protein-coupled receptor (GPCR). With its potent neuroprotective and anti-inflammatory effects, this peptide represents a promising avenue for the development of therapeutic strategies to potentially cure or at least slow the progression of neurodegenerative disorders. Beyond the canonical G protein signal effectors, GPCRs are also coupled to a multitude of intracellular signaling pathways that can be independently activated by biased ligands, thereby expanding vastly the potential for discovering new drugs...
April 25, 2018: Biochemical Pharmacology
Grazia Maugeri, Agata Grazia D'Amico, Daniela Maria Rasà, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two related peptides acting as neurotransmitters/neuromodulators in central and peripheral nervous system. They are also involved in cancer showing a controversial role. Particulary, they are implicated in neuroblastoma differentiation (NB). This pediatric tumor can evolve to a malignant metastatic disease or spontaneously regress towards a benign form, known as ganglioneuroblastoma/ganglioneuroma. A negative hallmark of neoplasia progression is represented by hypoxic microenvironment...
April 17, 2018: Neuropeptides
Salah A Baker, Bernard T Drumm, Caroline A Cobine, Kathleen D Keef, Kenton M Sanders
Gastrointestinal motility is coordinated by enteric neurons. Both inhibitory and excitatory motor neurons innervate the syncytium consisting of smooth muscle cells (SMCs) interstitial cells of Cajal (ICC) and PDGFRα+ cells (SIP syncytium). Confocal imaging of mouse small intestines from animals expressing GCaMP3 in ICC were used to investigate inhibitory neural regulation of ICC in the deep muscular plexus (ICC-DMP). We hypothesized that Ca2+ signaling in ICC-DMP can be modulated by inhibitory enteric neural input...
2018: Frontiers in Physiology
Xavier Peyrassol, Toon Laeremans, Vannessa Lahura, Maja Debulpaep, Hassan El Hassan, Jan Steyaert, Marc Parmentier, Ingrid Langer
Multi-membrane spanning proteins, such as G protein-coupled receptors (GPCRs) and ion channels, are extremely difficult to purify as native proteins. Consequently, the generation of antibodies that recognize the native conformation can be challenging. By combining genetic immunization, phage display, and biopanning, we identified a panel of monovalent antibodies (nanobodies) targeting the vasoactive intestinal peptide receptor 1 (VPAC1) receptor. The nine unique nanobodies that were classified into four different families based on their CDR3 amino acid sequence and length, were highly specific for the human receptor and bind VPAC1 with moderate affinity...
2018: Frontiers in Endocrinology
Huynh Nhu Mai, Yoon Hee Chung, Eun-Joo Shin, Naveen Sharma, Ji Hoon Jeong, Choon-Gon Jang, Kuniaki Saito, Toshitaka Nabeshima, Dora Reglodi, Hyoung-Chun Kim
IL-6 has been recognized as an anticonvulsant against certain neuroexcitotoxicities. We aimed to investigate on the interactive role between IL-6 and PACAP in cocaine-induced kindling behaviors. Although we found that cocaine (45 mg/kg, i.p./day x 5) significantly increased IL-6 and TNF-α expression, it resulted in a decrease in IFN-γ expression. We observed that the cocaine-induced increase in IL-6 expression was more pronounced than that in TNF-α expression. Genetic depletion of IL-6 significantly activated cocaine kindling behaviors...
April 16, 2018: Food and Chemical Toxicology
Takahiro Hirabayashi, Tomoya Nakamachi, Seiji Shioda
Pituitary adenylate-cyclase-activating polypeptide (PACAP) is a 27- or 38-amino acid neuropeptide, which belongs to the vasoactive intestinal polypeptide (VIP)/glucagon/secretin family. PACAP shows particularly high homology (~ 68%) to VIP. Because of the high homology of the amino acid sequences of PACAP and VIP, these peptides share three class B-G-protein coupled receptors: the PAC1-Receptor (PAC1-R), the VPAC1-Receptor (VPAC1-R) and VPAC2-Receptor (VPAC2-R). These receptors have high homology to each other, and their high homology is utilized for these discoveries...
April 4, 2018: Journal of Headache and Pain
Dora Reglodi, Anita Illes, Balazs Opper, Eszter Schafer, Andrea Tamas, Gabriella Horvath
Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide with widespread occurrence throughout the body including the gastrointestinal system. In the small and large intestine, effects of PACAP on cell proliferation, secretion, motility, gut immunology and blood flow, as well as its importance in bowel inflammatory reactions and cancer development have been shown and reviewed earlier. However, no current review is available on the actions of PACAP in the stomach in spite of numerous data published on the gastric presence and actions of the peptide...
2018: Frontiers in Endocrinology
D Reglodi, A Tamas, A Jungling, A Vaczy, A Rivnyak, B D Fulop, E Szabo, A Lubics, T Atlasz
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide highly expressed in the central and peripheral nervous system, where it exerts several neuromodulatory functions and is an important trophic and protective factor. PACAP has been shown to activate several protective pathways, mainly through its specific PAC1 receptor and protein kinase A, C and MAP kinases downstream. It has been shown to have very potent neuroprotective actions against different neurotoxic agents both in vitro and in vivo...
March 28, 2018: Neurotoxicology
Adam Rivnyak, Peter Kiss, Andrea Tamas, Dorottya Balogh, Dora Reglodi
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with widespread occurrence and diverse biological effects. Among its several different effects, of special importance is the action of PACAP on neuronal proliferation, differentiation and migration, and neuroprotection. The neuroprotective mechanism of PACAP is both direct and indirect, via neuronal and non-neuronal cells. Several research groups have performed transcriptomic and proteomic analysis on PACAP-mediated genes and proteins...
March 29, 2018: International Journal of Molecular Sciences
Giuseppe Musumeci, Gian Marco Leggio, Rubina Marzagalli, Ghaith Al-Badri, Filippo Drago, Alessandro Castorina
Following peripheral nerve injury, dysregulations of certain non-coding microRNAs (miRNAs) occur in Schwann cells. Whether these alterations are the result of local inflammation and/or correlate with perturbations in the expression profile of the protective vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) system is currently unknown. To address these issues, we aimed at profiling the expression of selected miRNAs in the rat RT4 Schwann cell line. Cells exposed to lipopolysaccharide (LPS), to mimic the local inflammatory milieu, were appraised by real-time qPCR, Western blot and ELISAs...
March 25, 2018: International Journal of Molecular Sciences
Michael Allen Thoene, Liliana Rytel, Ewa Dzika, Ignacy Gonkowski, Andrzej Włodarczyk, Joanna Wojtkiewicz
BACKGROUND: The neurochemistry of hepatic nerve fibers was investigated in large animal models after dietary exposure to the endocrine disrupting compound known as bisphenol A. MATERIALS AND METHODS: Antibodies against neuronal peptides were used to study changes in hepatic nerve fibers after exposure to bisphenol A (BPA) at varying concentrations using standard immunofluorescence techniques. The neuropeptides investigated were substance P (SP), galanin (GAL), pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene regulated peptide (CGRP) and cocaine & amphetamine regulated transcript (CART)...
March 23, 2018: Folia Morphologica (Warsz)
Bernadett Mosdósi, Kata Bölcskei, Zsuzsanna Helyes
BACKGROUND: Raynaud's phenomenon (RP) is a functional vascular disease, presenting with recurrent episodes of ischemia of extremities in response to cold and emotional stress. Investigating cutaneous microcirculation is an important tool in understanding the complex neuro-immuno-vascular interactions in its pathophysiological mechanisms. Since there is no available data on vascular responsiveness in RP in the paediatric population, we investigated skin perfusion and heat-induced hyperaemia in comparison with clinical severity and laboratory parameters of the disease...
March 23, 2018: Pediatric Rheumatology Online Journal
Chengyuan Lin, Jin Bai, Mulan He, Anderson O L Wong
In this study, structural analysis of grass carp prolactin (PRL) gene was performed and the signaling mechanisms for pituitary adenylate cyclase-activating peptide (PACAP) regulation of PRL promoter activity were investigated. In αT3-1 cells, PRL promoter activity could be induced by oPACAP38 which was blocked by PACAP antagonist but not the VIP antagonist. The stimulatory effect of oPACAP38 was mimicked by activation of AC/cAMP and voltage-sensitive Ca2+ channel (VSCC) signaling, or induction of Ca2+ entry...
March 15, 2018: Scientific Reports
James A Waschek, Serapio M Baca, Simon Akerman
The discovery that intravenous (IV) infusions of the neuropeptide PACAP-38 (pituitary adenylyl cyclase activating peptide-38) induced delayed migraine-like headaches in a large majority of migraine patients has resulted in considerable excitement in headache research. In addition to suggesting potential therapeutic targets for migraine, the finding provides an opportunity to better understand the pathological events from early events (aura) to the headache itself. Although PACAP-38 and the closely related peptide VIP (vasoactive intestinal peptide) are well-known as vasoactive molecules, the dilation of cranial blood vessels per se is no longer felt to underlie migraine headaches...
March 13, 2018: Journal of Headache and Pain
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