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https://www.readbyqxmd.com/read/28475285/involvement-of-neurone-glia-neurone-neurone-communications-via-gap-junctions-in-synchronised-activity-of-kndy-neurones
#1
K Ikegami, S Minabe, N Ieda, T Goto, A Sugimoto, S Nakamura, N Inoue, S Oishi, A D Maturana, M Sanbo, M Hirabayashi, K-I Maeda, H Tsukamura, Y Uenoyama
Pulsatile secretion of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone is indispensable for puberty onset and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, kisspeptin, encoded by Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, are a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is thought to be required for pulsatile GnRH secretion...
May 5, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28464209/alanine-scan-of-the-opioid-peptide-dynorphin-b-amide
#2
Anand A Joshi, Thomas F Murray, Jane V Aldrich
To date structure-activity relationship (SAR) studies of the dynorphins (Dyn), endogenous peptides for kappa opioid receptors (KOR), have focused almost exclusively on Dyn A with minimal studies on Dyn B. While both Dyn A and Dyn B have identical N-terminal sequences, their C-terminal sequences differ which could result in differences in pharmacological activity. We performed an alanine scan of the non-glycine residues up through residue 11 of Dyn B amide to explore the role of these side chains in the activity of Dyn B...
May 2, 2017: Biopolymers
https://www.readbyqxmd.com/read/28449351/long-term-plasticity-of-corticostriatal-synapses-is-modulated-by-pathway-specific-co-release-of-opioids-through-kappa-opioid-receptors
#3
Sarah L Hawes, Armando G Salinas, David M Lovinger, Kim T Blackwell
Synaptic plasticity in striatum adjusts behaviour adaptively during skill learning, or maladaptively in the case of addiction. Just as dopamine plays a critical role in synaptic plasticity underlying normal skill learning and addiction, endogenous and exogenous opiates also modulate learning and addiction-related striatal plasticity. Though the role of opioid receptors in long-term depression in striatum has been characterized, their effect on long-term potentiation (LTP) remains unknown. In particular, direct pathway (Dopamine D1 Receptor containing; D1R) - spiny projection neurons (SPNs) co-release the opioid neuropeptide dynorphin, which acts at presynaptic kappa opioid receptors (KORs) on dopaminergic afferents and can negatively regulate dopamine release...
April 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28444173/tac1-signaling-is-required-for-sexual-maturation-and-responsiveness-of-gnrh-neurons-to-kisspeptin-in-the-male-mouse
#4
Caroline A Maguire, Yong Bhum Song, Min Wu, Silvia León, Rona S Carroll, Meenakshi Alreja, Ursula B Kaiser, Víctor M Navarro
The tachykinins substance P (SP) and neurokinin A (NKA) (Tac1) have emerged as novel regulators of kisspeptin/GnRH release. Recently, we documented that SP modulates reproductive function in the female mouse. Here, we extended this characterization to the male mouse. Tac1-/- male mice showed delayed puberty onset. They also presented significantly decreased expression levels of Pdyn (dynorphin) and Nos1 (nitric oxide synthase) in the mediobasal hypothalamus and elevated Gnrh1 levels. Unexpectedly, the response of Tac1-/- mice to central kisspeptin or senktide (neurokinin B receptor -NK3R- agonist) administration was significantly decreased compared with controls, despite the preserved ability of GnRH neurons to stimulate LH release as demonstrated by central NMDA administration, suggesting a deficit at the GnRH neuron level...
April 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28442370/modulation-of-drug-choice-by-extended-drug-access-and-withdrawal-in-rhesus-monkeys-implications-for-negative-reinforcement-as-a-driver-of-addiction-and-target-for-medications-development
#5
REVIEW
S Stevens Negus, Matthew L Banks
Chronic drug exposure is hypothesized to recruit negative reinforcement processes that increase the magnitude and alter the mechanisms of drug reinforcement. Candidate substrates of negative reinforcement include increased signaling via stress-related neurotransmitters such as corticotropin releasing factor (CRF, acting at CRF receptors) or dynorphin (acting at kappa opioid receptors) and/or decreased signaling via reward-related neurotransmitters such as dopamine. Determinants of drug reinforcement can be examined with choice procedures, in which subjects choose between a drug of interest (e...
April 22, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28431971/influence-of-stress-associated-with-chronic-alcohol-exposure-on-drinking
#6
REVIEW
Howard C Becker
Stress is commonly regarded as an important trigger for relapse and a significant factor that promotes increased motivation to drink in some individuals. However, the relationship between stress and alcohol is complex, likely changing in form during the transition from early moderated alcohol use to more heavy uncontrolled alcohol intake. A growing body of evidence indicates that prolonged excessive alcohol consumption serves as a potent stressor, producing persistent dysregulation of brain reward and stress systems beyond normal homeostatic limits...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28425121/role-of-the-dynorphin-kappa-opioid-receptor-system-in-the-motivational-effects-of-ethanol
#7
Rachel I Anderson, Howard C Becker
Evidence has demonstrated that dynorphin (DYN) and the kappa opioid receptor (KOR) system contribute to various psychiatric disorders, including anxiety, depression, and addiction. More recently, this endogenous opioid system has received increased attention as a potential therapeutic target for treating alcohol use disorders. In this review, we provide an overview and synthesis of preclinical studies examining the influence of alcohol (ethanol) exposure on DYN/KOR expression and function, as well as studies examining the effects of DYN/KOR manipulation on ethanol's rewarding and aversive properties...
April 20, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28376659/kappa-opioid-receptor-antagonists-a-possible-new-class-of-therapeutics-for-migraine-prevention
#8
Jennifer Y Xie, Milena De Felice, Caroline M Kopruszinski, Nathan Eyde, Justin LaVigne, Bethany Remeniuk, Pablo Hernandez, Xu Yue, Naomi Goshima, Michael Ossipov, Tamara King, John M Streicher, Edita Navratilova, David Dodick, Hugh Rosen, Ed Roberts, Frank Porreca
Background Stress is the most commonly reported migraine trigger. Dynorphin, an endogenous opioid peptide acting preferentially at kappa opioid receptors (KORs), is a key mediator of stress responses. The aim of this study was to use an injury-free rat model of functional cephalic pain with features of migraine and medication overuse headache (MOH) to test the possible preventive benefit of KOR blockade on stress-induced cephalic pain. Methods Following sumatriptan priming to model MOH, rats were hyper-responsive to environmental stress, demonstrating delayed cephalic and extracephalic allodynia and increased levels of CGRP in the jugular blood, consistent with commonly observed clinical outcomes during migraine...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28363796/structure-constrained-endomorphin-analogs-display-differential-antinociceptive-mechanisms-in-mice-after-spinal-administration
#9
Yuan Wang, Jingjing Zhou, Xin Liu, Long Zhao, Zhaojuan Wang, Xianghui Zhang, Kezhou Wang, Linqing Wang, Rui Wang
We previously reported a series of novel endomorphin analogs with unnatural amino acid modifications. These analogs display good binding affinity and functional activity toward the μ opioid receptor (MOP). In the present study, we further investigated the spinal antinociceptive activity of these compounds. The analogs were potent in several nociceptive models. Opioid antagonists and antibodies against several endogenous opioid peptides were used to determine the mechanisms of action of these peptides. Intrathecal pretreatment with naloxone and β-funaltrexamine (β-FNA) effectively inhibited analog-induced analgesia, demonstrating that activity of the analogs is regulated primarily through MOP...
May 2017: Peptides
https://www.readbyqxmd.com/read/28350441/chemical-probes-unravel-an-antimicrobial-defense-response-triggered-by-binding-of-the-human-opioid-dynorphin-to-a-bacterial-sensor-kinase
#10
Megan H Wright, Christian Fetzer, Stephan A Sieber
Host-microbe communication via small molecule signals is important for both symbiotic and pathogenic relationships, but is often poorly understood at the molecular level. Under conditions of host stress, levels of the human opioid peptide dynorphin are elevated, triggering virulence in the opportunistic pathogenic bacterium Pseudomonas aeruginosa via an unknown pathway. Here we apply a multilayered chemical biology strategy to unravel the mode of action of this putative interkingdom signal. We designed and applied dynorphin-inspired photoaffinity probes to reveal the protein targets of the peptide in live bacteria via chemical proteomics...
April 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28336495/genetic-variation-and-epigenetic-modification-of-the-prodynorphin-gene-in-peripheral-blood-cells-in-alcoholism
#11
Claudio D'Addario, Klementy Shchetynsky, Mariangela Pucci, Carlo Cifani, Agneta Gunnar, Vladana Vukojević, Leonid Padyukov, Lars Terenius
Dynorphins are critically involved in the development, maintenance and relapse of alcoholism. Alcohol-induced changes in the prodynorphin gene expression may be influenced by both gene polymorphisms and epigenetic modifications. The present study of human alcoholics aims to evaluate DNA methylation patterns in the prodynorphin gene (PDYN) promoter and to identify single nucleotide polymorphisms (SNPs) associated with alcohol dependence and with altered DNA methylation. Genomic DNA was isolated from peripheral blood cells of alcoholics and healthy controls, and DNA methylation was studied in the PDYN promoter by bisulfite pyrosequencing...
March 21, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28328155/does-dynorphin-play-a-role-in-the-onset-of-puberty-in-female-sheep
#12
J A Lopez, M N Bedenbaugh, R B McCosh, P W Weems, L J Meadows, B Wisman, L M Coolen, R L Goodman, S M Hileman
Puberty onset involves increased gonadotrophin-release (GnRH) release as a result of decreased sensitivity to oestrogen (E2 )-negative feedback. Because GnRH neurones lack E2 receptor α, this pathway must contain interneurones. One likely candidate is KNDy neurones (kisspeptin, neurokinin B, dynorphin). The overarching hypothesis of the present study was that the prepubertal hiatus in luteinising hormone (LH) release involves reduced kisspeptin and/or heightened dynorphin input. We first tested the specific hypothesis that E2 would reduce kisspeptin-immunopositive cell numbers and increase dynorphin-immunopositive cell numbers...
December 2016: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28327597/molecular-signaling-underlying-bulleyaconitine-a-baa-induced-microglial-expression-of-prodynorphin
#13
Teng-Fei Li, Hai-Yun Wu, Yi-Rui Wang, Xin-Yan Li, Yong-Xiang Wang
Bulleyaconitine (BAA) has been shown to possess antinociceptive activities by stimulation of dynorphin A release from spinal microglia. This study investigated its underlying signal transduction mechanisms. The data showed that (1) BAA treatment induced phosphorylation of CREB (rather than NF-κB) and prodynorphin expression in cultured primary microglia, and antiallodynia in neuropathy, which were totally inhibited by the CREB inhibitor KG-501; (2) BAA upregulated phosphorylation of p38 (but not ERK or JNK), and the p38 inhibitor SB203580 (but not ERK or JNK inhibitor) and p38β gene silencer siRNA/p38β (but not siRNA/p38α) completely blocked BAA-induced p38 phosphorylation and/or prodynorphin expression, and antiallodynia; (3) BAA stimulated cAMP production and PKA phosphorylation, and the adenylate cyclase inhibitor DDA and PKA inhibitor H-89 entirely antagonized BAA-induced prodynorphin expression and antiallodynia; (4) The Gs-protein inhibitor NF449 completely inhibited BAA-increased cAMP level, prodynorphin expression and antiallodynia, whereas the antagonists of noradrenergic, corticotrophin-releasing factor, A1 adenosine, formyl peptide, D1/D2 dopamine, and glucagon like-peptide-1 receptors failed to block BAA-induced antiallodynia...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324006/effects-of-season-and-estradiol-on-kndy-neuron-peptides-colocalization-with-d2-dopamine-receptors-and-dopaminergic-inputs-in-the-ewe
#14
Peyton Weems, Jeremy Smith, Iain J Clarke, Lique M Coolen, Robert L Goodman, Michael N Lehman
Seasonal reproduction in sheep is primarily due to a dramatic increase in the ability of estradiol (E2) to inhibit the pulsatile secretion of gonadotropin-releasing hormone (GnRH) during the nonbreeding season [anestrus (ANS)]. Recent findings suggest that kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in conveying this negative feedback influence, with dopaminergic projections from the retrochiasmatic area acting upon KNDy cells to decrease kisspeptin release and thus inhibit GnRH pulses...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28303403/hypocretin-orexin-and-plastic-adaptations-associated-with-drug-abuse
#15
Corey Baimel, Stephanie L Borgland
Dopamine neurons in the ventral tegmental area (VTA) are a critical part of the neural circuits that underlie reward learning and motivation. Dopamine neurons send dense projections throughout the brain and recent observations suggest that both the intrinsic properties and the functional output of dopamine neurons are dependent on projection target and are subject to neuromodulatory influences. Lateral hypothalamic hypocretin (also termed orexin) neurons project to the VTA and contain both hypocretin and dynorphin peptides in the same dense core vesicles suggesting they may be co-released...
March 17, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28288109/in-silico-design-of-novel-probes-for-the-atypical-opioid-receptor-mrgprx2
#16
Katherine Lansu, Joel Karpiak, Jing Liu, Xi-Ping Huang, John D McCorvy, Wesley K Kroeze, Tao Che, Hiroshi Nagase, Frank I Carroll, Jian Jin, Brian K Shoichet, Bryan L Roth
The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small-molecule MRGPRX2 agonists, selective nanomolar-potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found that many opioid compounds activated MRGPRX2, including (-)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan, and the prodynorphin-derived peptides dynorphin A, dynorphin B, and α- and β-neoendorphin...
May 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28251550/the-mystery-of-puberty-initiation-genetics-and-epigenetics-of-idiopathic-central-precocious-puberty-icpp
#17
REVIEW
Sofia Leka-Emiri, George P Chrousos, Christina Kanaka-Gantenbein
Puberty is a major developmental stage. Damaging mutations, considered as "mistakes of nature", have contributed to the unraveling of the networks implicated in the normal initiation of puberty. Genes involved in the abnormal hypothalamic-pituitary-gonadal (HPG) axis development, in the normosmic idiopathic hypogonadotropic hypogonadism (nIHH), in the X-linked or autosomal forms of Kallmann syndrome and in precocious puberty have been identified (GNRH1, GNRHR, KISS1, GPR54, FGFR1, FGF8, PROK2, PROKR2, TAC3, TACR3, KAL1, PROK2, PROKR2, CHD7, LEP, LEPR, PC1, DAX1, SF-1, HESX-1, LHX3, PROP-1)...
March 1, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28242307/molecular-identification-of-the-dyn-kor-system-and-its-potential-role-in-the-reproductive-axis-of-goldfish
#18
Yali Liu, Shuisheng Li, Qing Wang, Yu Chen, Xin Qi, Yun Liu, Xiaochun Liu, Haoran Lin, Yong Zhang
To ascertain the significance of the dynorphin/kappa-opioid receptor (Dyn/Kor) system in fish reproduction, prodynorphin (pdyn) cDNA was cloned from goldfish. Two Dyn peptides (DynA and DynB) are present in the goldfish prodynorphin precursor. Both DynA and DynB are biologically active as they are able to functionally interact with the goldfish Kor expressed in cultured eukaryotic cells to suppress forskolin-induced CRE promoter activity. RT-PCR analysis showed that pdyn is widely expressed in brain regions, with the highest expression in hypothalamus...
February 24, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28219695/inhibitory-effects-of-dynorphin-3-14-on-the-lipopolysaccharide-induced-toll-like-receptor-4-signalling-pathway
#19
Siti Sarah Fazalul Rahiman, Michael Morgan, Paul Gray, Paul Nicholas Shaw, Peter John Cabot
Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells...
February 20, 2017: Peptides
https://www.readbyqxmd.com/read/28178514/projection-target-defined-effects-of-orexin-and-dynorphin-on-vta-dopamine-neurons
#20
Corey Baimel, Benjamin K Lau, Min Qiao, Stephanie L Borgland
Circuit-specific signaling of ventral tegmental area (VTA) dopamine neurons drives different aspects of motivated behavior, but the neuromodulatory control of these circuits is unclear. We tested the actions of co-expressed lateral hypothalamic peptides, orexin A (oxA) and dynorphin (dyn), on projection-target-defined dopamine neurons in mice. We determined that VTA dopamine neurons that project to the nucleus accumbens lateral shell (lAcbSh), medial shell (mAcbSh), and basolateral amygdala (BLA) are largely non-overlapping cell populations with different electrophysiological properties...
February 7, 2017: Cell Reports
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