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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
Tomoya Nakamachi, Eri Kamata, Ayano Tanigawa, Norifumi Konno, Seiji Shioda, Kouhei Matsuda
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multipotent neuropeptide with an amino acid sequence that is well conserved among vertebrates. In teleosts, including zebrafish, the PACAP gene (adcyap1) has been duplicated to yield adcyap1a (coding PACAP1) and adcyap1b (coding PACAP2). This study aims to determine the distribution of these PACAPs and their mRNAs in zebrafish. We generated a zebrafish PACAP2-specific antibody. Using real-time PCR, we observed that adcyap1b mRNA was primarily localized in the brain, with the highest level in the telencephalon, followed by the diencephalon...
March 10, 2018: Peptides
N Cabezas-Llobet, L Vidal-Sancho, M Masana, A Fournier, J Alberch, D Vaudry, X Xifró
Deficits in hippocampal synaptic plasticity result in cognitive impairment in Huntington's disease (HD). Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts neuroprotective actions, mainly through the PAC1 receptor. However, the role of PACAP in cognition is poorly understood, and no data exists in the context of Huntington's disease (HD). Here, we investigated the ability of PACAP receptor stimulation to enhance memory development in HD. First, we observed a hippocampal decline of all three PACAP receptor expressions, i...
March 10, 2018: Molecular Neurobiology
Lars Edvinsson, János Tajti, Levente Szalárdy, László Vécsei
Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding its localization, PACAP has been observed in the sensory trigeminal ganglion (TG), in the parasympathetic sphenopalatine (SPG) and otic ganglia (OTG), and in the brainstem trigeminocervical complex. Immunohistochemistry has shown PACAP-38 in numerous cell bodies of SPG/OTG, co-stored with vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and, to a minor degree, with choline acetyltransferase...
March 9, 2018: Journal of Headache and Pain
Philip R Holland, Mads Barloese, Jan Fahrenkrug
The interaction between sleep and primary headaches has gained considerable interest due to their strong, bidirectional, clinical relationship. Several primary headaches demonstrate either a circadian/circannual rhythmicity in attack onset or are directly associated with sleep itself. Migraine and cluster headache both show distinct attack patterns and while the underlying mechanisms of this circadian variation in attack onset remain to be fully explored, recent evidence points to clear physiological, anatomical and genetic points of convergence...
March 5, 2018: Journal of Headache and Pain
Dora Reglodi, Alexandra Vaczy, Eloísa Rubio-Beltran, Antoinette MaassenVanDenBrink
Pituitary adenylate cyclase activating polypeptide (PACAP) is an ubiquitous peptide involved, among others, in neurodevelopment, neuromodulation, neuroprotection, neurogenic inflammation and nociception. Presence of PACAP and its specific receptor, PAC1, in the trigeminocervical complex, changes of PACAP levels in migraine patients and the migraine-inducing effect of PACAP injection strongly support the involvement of PACAP/PAC1 receptor in migraine pathogenesis. While antagonizing PAC1 receptor is a promising therapeutic target in migraine, the diverse array of PACAP's functions, including protection in ischemic events, requires that the cost-benefit of such an intervention is well investigated by taking all the beneficial effects of PACAP into account...
March 2, 2018: Journal of Headache and Pain
Pan Qi, Jingang Zhong, Xiao Ma, Shiping Li, Ying Li
BACKGROUND: The self-developed portable surface plasmon resonance (SPR) biosensor was used in the quantitative detection and kinetic study of pituitary adenylate cyclase-activating polypeptide (PACAP), as the existing detection methods were complicated, with a long detection period, high-cost instrument, and sample needing to be labeled. METHODS: After preparing SPR biochip, the direct detection proceeded in an immune reaction detection between the PACAP samples with concentrations of 0...
January 1, 2018: Clinical Laboratory
Margit Solymar, Ivan Ivic, Marta Balasko, Balazs D Fulop, Gabor Toth, Andrea Tamas, Gyongyver Reman, Akos Koller, Dora Reglodi
BACKGROUND: Short-lasting hyperglycaemia occurs frequently in prediabetes and poorly controlled diabetes mellitus leading to vascular damage. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to play a protective role in vascular complications of diabetes; moreover, antioxidant effects of PACAP were also described. Therefore, we hypothesized that PACAP exerts protective effects in short-term hyperglycaemia-induced vascular dysfunctions. METHODS: After short-term hyperglycaemia, acetylcholine-induced and sodium nitroprusside-induced vascular relaxation of mouse carotid arteries were tested with a myograph with or without the presence of PACAP or superoxide dismutase...
February 1, 2018: Diabetes & Vascular Disease Research
Inger Jansen-Olesen, Sara Hougaard Pedersen
BACKGROUND: In migraineurs pituitary adenylate cyclase activating peptide1-38 (PACAP1-38) is a potent migraine provoking substance and the accompanying long lasting flushing suggests degranulation of mast cells. Infusion of the closely related vasoactive intestinal peptide (VIP) either induces headache or flushing. This implicates the pituitary adenylate cyclase activating peptide type I receptor (PAC1) to be involved in the pathophysiology of PACAP1-38 provoked headaches. Here we review studies characterizing the effects of mainly PACAP but also of VIP on cerebral and meningeal arteries and mast cells...
February 20, 2018: Journal of Headache and Pain
Ghaith Al-Badri, Gian Marco Leggio, Giuseppe Musumeci, Rubina Marzagalli, Filippo Drago, Alessandro Castorina
Dipeptidyl peptidase IV (DPP-IV) is a serine protease best known for its role in inactivating glucagon-like peptide-1 (GLP-1), pituitary adenylate cyclase-activating polypeptide (PACAP) and glucose-dependent insulinotropic peptide (GIP), three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal. Owing to the relationship between DPP-IV and these peptides, inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients. Nonetheless, increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component, potentially through its non-incretin activities on immune cells...
January 2018: Neural Regeneration Research
Jan Fahrenkrug, Birgitte Georg, Jens Hannibal, Henrik Løvendahl Jørgensen
The intraocular pressure of mice displays a daily rhythmicity being highest during the dark period. The present study was performed to elucidate the role of the circadian clock and light in the diurnal and the circadian variations in intraocular pressure in mice, by using animals with disrupted clock function (VPAC2 receptor knockout mice) or impaired light information to the clock (PACAP knockout mice). In wildtype mice, intraocular pressure measured under light/dark conditions showed a statistically significant 24 h sinusoidal rhythm with nadir during the light phase and peak during the dark phase...
February 8, 2018: Experimental Eye Research
Susanne Grässel, Dominique Muschter
Joint tissues like synovium, articular cartilage, meniscus and subchondral bone, are targets for neuropeptides. Resident cells of these tissues express receptors for various neuroendocrine-derived peptides including proopiomelanocortin (POMC)-derived peptides, i.e., α-melanocyte-stimulating hormone (α-MSH), adrenocorticotropin (ACTH) and β-endorphin (β-ED), and sympathetic neuropeptides like vasoactive intestinal peptide (VIP) and neuropeptide y (NPY). Melanocortins attained particular attention due to their immunomodulatory and anti-inflammatory effects in several tissues and organs...
January 26, 2018: International Journal of Molecular Sciences
Ichiro Takasaki, Ai Watanabe, Masafumi Yokai, Yurie Watanabe, Daichi Hayakawa, Ryota Nagashima, Mamoru Fukuchi, Takuya Okada, Naoki Toyooka, Atsuro Miyata, Hiroaki Gouda, Takashi Kurihara
Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are present in the spinal dorsal horn and dorsal root ganglia, suggesting an important role of PACAP signaling systems in the modulation of spinal nociceptive transmission. Previously, we found that intrathecal (i.t.) injection of PACAP or maxadilan, a selective PACAP type I (PAC1) receptor agonist, induced transient aversive responses followed by a long-lasting mechanical allodynia in mice, suggesting that PACAP-PAC1 receptor systems are involved in chronic pain and that selective PAC1 antagonists may become a new class of analgesics...
January 23, 2018: Journal of Pharmacology and Experimental Therapeutics
Zsolt Sarszegi, Dora Szabo, Balazs Gaszner, Attila Konyi, Dora Reglodi, Jozsef Nemeth, Beata Lelesz, Beata Polgar, Adel Jungling, Andrea Tamas
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic and multifunctional neuropeptide having neurotrophic, neuroprotective, and general cytoprotective actions in a variety of tissues based on its anti-apoptotic, anti-inflammatory, and antioxidant effects. Several studies have demonstrated its cardioprotective effects in vitro and in various animal models. However, few data are available on the presence of PACAP in human cardiac tissues and its role in the pathomechanism and progression of different cardiac disorders, particularly heart failure...
January 20, 2018: Journal of Molecular Neuroscience: MN
Adam J Kirry, Matthew R Herbst, Sarah E Poirier, Michelle M Maskeri, Amy C Rothwell, Robert C Twining, Marieke R Gilmartin
A genetic polymorphism within the gene encoding the pituitary adenylate-cyclase activating polypeptide (PACAP) receptor type I (PAC1R) has recently been associated with hyper-reactivity to threat-related cues in women, but not men, with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide, whose role in mediating adaptive physiological stress responses is well established. Far less is understood about the contribution of PACAP signaling in emotional learning and memory, particularly the encoding of fear to discrete cues...
January 15, 2018: Neuropharmacology
Violeta Georgieva Tsonkova, Fredrik Wolfhagen Sand, Xenia Asbæk Wolf, Lars Groth Grunnet, Anna Kirstine Ringgaard, Camilla Ingvorsen, Louise Winkel, Mark Kalisz, Kevin Dalgaard, Christine Bruun, Johannes Josef Fels, Charlotte Helgstrand, Sven Hastrup, Fredrik Kryh Öberg, Erik Vernet, Michael Paolo Bastner Sandrini, Allan Christian Shaw, Carsten Jessen, Mads Grønborg, Jacob Hald, Hanni Willenbrock, Dennis Madsen, Rasmus Wernersson, Lena Hansson, Jan Nygaard Jensen, Annette Plesner, Tomas Alanentalo, Maja Borup Kjær Petersen, Anne Grapin-Botton, Christian Honoré, Jonas Ahnfelt-Rønne, Jacob Hecksher-Sørensen, Philippe Ravassard, Ole D Madsen, Claude Rescan, Thomas Frogne
OBJECTIVE: To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. METHODS: EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice...
December 19, 2017: Molecular Metabolism
Arsalan U Syed, Masayo Koide, Joseph E Brayden, George C Wellman
Activation of ATP-sensitive potassium (KATP ) channels in arterial smooth muscle (ASM) contributes to vasodilation evoked by a variety of endogenous and exogenous compounds. Although controversial, activation of KATP channels by neuropeptides such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP) in the trigeminovascular system, including the middle meningeal artery (MMA), has been linked to migraine headache. The objective of the current study was to determine if ongoing KATP channel activity also influences MMA diameter...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
M Feher, B Gaszner, A Tamas, A L Gil-Martinez, E Fernandez-Villalba, M T Herrero, D Reglodi
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-known neuropeptide with strong neurotrophic and neuroprotective effects. PACAP exerts its protective actions via three G protein-coupled receptors: the specific Pac1 receptor (Pac1R) and the Vpac1/Vpac2 receptors, the neuroprotective effects being mainly mediated by the Pac1R. The protective role of PACAP in models of Parkinson's disease and other neurodegenerative diseases is now well-established in both in vitro and in vivo studies. PACAP and its receptors occur in the mammalian brain, including regions associated with Parkinson's disease...
December 11, 2017: Neurotoxicity Research
Zohra M Kakall, Paul M Pilowsky, Melissa Mj Farnham
BACKGROUND AND PURPOSE: Intermittent hypoxia causes a persistent increase in sympathetic activity, which progresses to hypertension in chronic conditions such as obstructive sleep apnea (OSA). Pituitary adenylate cyclase activating polypeptide (PACAP) is an excitatory neurotransmitter that causes long-lasting sympathetic excitation. We aimed to determine if intermittent activation of the rostral ventrolateral medulla (RVLM) causes PACAP-mediated elevation of sympathetic nerve activity (sSNA), termed sympathetic long-term facilitation (sLTF)...
December 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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