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Acid-sensing ion channels

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https://www.readbyqxmd.com/read/29044608/nutrient-sensing-in-pancreatic-islets-lessons-from-congenital-hyperinsulinism-and-monogenic-diabetes
#1
REVIEW
Ming Lu, Changhong Li
Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM))...
October 16, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29044528/endomorphins-potentiate-asic-currents-and-enhance-the-lactic-acid-mediated-increase-in-arterial-blood-pressure-effects-amplified-in-hindlimb-ischemia
#2
Mohamed Farrag, Julie K Drobish, Henry L Puhl, Joyce S Kim, Paul B Herold, Marc P Kaufman, Victor Ruiz-Velasco
Chronic muscle ischemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex...
October 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29039242/computational-elucidation-mutational-and-hot-spot-based-designing-of-potential-inhibitors-against-human-acid-sensing-ion-channels-hasic-1a-to-treatment-of-various-physiological-conditions
#3
Anurag Singh Chauhan, Md Yousuf Ansari, Rani Mansuri, Manas Ranjan Dikhit, Vahab Ali, Ganesh Chandra Sahoo, Pradeep Das
Acid-sensing ion channels (ASICs) are ligand/proton-gated ion channels belonging to the family of the degenerin/epithelial Na(+) channel (DEG/ENaC). They function as a sodium-selective pore for Ca(2+) entry into neuronal cells during pathological conditions. The blocking of this channel has therapeutic importance, because at basal physiological pH (7.2), it is in a closed state and under a more acidic condition, and the ASIC1a ion channel is activated. To investigate the different states of the hASIC1a channel based on mutational analysis, structure based virtual screening and molecular dynamics simulation studies...
October 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29036449/resveratrol-attenuates-bone-cancer-pain-through-regulating-the-expression-levels-of-asic3-and-activating-cell-autophagy
#4
Haili Zhu, Jieqiong Ding, J Wu, Tingting Liu, Jing Liang, Qiong Tang, Ming Jiao
Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4-L6 dorsal root ganglion...
October 3, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29033788/zinc-as-a-neuromodulator-in-the-central-nervous-system-with-a-focus-on-the-olfactory-bulb
#5
REVIEW
Laura J Blakemore, Paul Q Trombley
The olfactory bulb (OB) is central to the sense of smell, as it is the site of the first synaptic relay involved in the processing of odor information. Odor sensations are first transduced by olfactory sensory neurons (OSNs) before being transmitted, by way of the OB, to higher olfactory centers that mediate olfactory discrimination and perception. Zinc is a common trace element, and it is highly concentrated in the synaptic vesicles of subsets of glutamatergic neurons in some brain regions including the hippocampus and OB...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29027122/hi1a-as-a-novel-neuroprotective-agent-for-ischemic-stroke-by-inhibition-of-acid-sensing-ion-channel-1a
#6
Yandong Ren, Chengchong Li, Jinlong Chang, Rui Wang, Yuhua Wang, Xiang-Ping Chu
Strokes are the second-leading cause of death worldwide, and the cellular and molecular mechanisms underlying stroke-induced brain damage are still uncertain. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA). However, rtPA has a narrow therapeutic timeframe of 3-4.5 h, and only approximately 5% of stroke patients can benefit from rtPA treatment. Neuroprotective agents, such as N-methyl-D-aspartate receptor antagonists, have shown great promise in preclinical studies...
October 13, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29025967/diminazene-is-a-slow-pore-blocker-of-acid-sensing-ion-channel-1a-asic1a
#7
Axel Schmidt, Giulia Rossetti, Sylvia Joussen, Stefan Grunder
Acid-sensing ion channels (ASICs) are neuronal receptors for extracellular protons. They contribute to the excitatory postsynaptic current and to the detection of painful acidosis. Moreover, they are activated during peripheral inflammation and acidosis associated with various neuronal disorders such as stroke and neuro-inflammation, rendering them interesting drug targets. Diminazene aceturate is a small molecule inhibitor of ASICs with a reported apparent affinity in the low micromolar range, making it an interesting lead compound...
October 12, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29019932/asic1a-promotes-acid-induced-autophagy-in-rat-articular-chondrocytes-through-the-ampk-foxo3a-pathway
#8
Beibei Dai, Fei Zhu, Yong Chen, Renpeng Zhou, Zhisen Wang, Yaya Xie, Xiaoshan Wu, Shengqin Zu, Ge Li, Jinfang Ge, Feihu Chen
Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H⁺-activated cation channels family. Our previous studies suggested that ASIC1a contributed to acid-induced rat articular chondrocytes autophagy. However, its potential mechanisms remain unclear. The present study demonstrated the effect of ASIC1a on rat articular chondrocytes autophagy and explored the underlying molecular mechanisms. The results demonstrated that ASIC1a contributed to acid-induced autophagy in rat articular chondrocytes, and which was associated with an increase in (Ca(2+))i, as indicated that acid-induced increases in mRNA and protein expression of LC3B-II and other autophagy-related markers were inhibited by ASIC1a-specific blocker, PcTx1 and calcium chelating agent, BAPTA-AM...
October 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28989662/aie-doped-poly-ionic-liquid-photonic-spheres-a-single-sphere-based-customizable-sensing-platform-for-the-discrimination-of-multi-analytes
#9
Wanlin Zhang, Ning Gao, Jiecheng Cui, Chen Wang, Shiqiang Wang, Guanxin Zhang, Xiaobiao Dong, Deqing Zhang, Guangtao Li
By simultaneously exploiting the unique properties of ionic liquids and aggregation-induced emission (AIE) luminogens, as well as photonic structures, a novel customizable sensing system for multi-analytes was developed based on a single AIE-doped poly(ionic liquid) photonic sphere. It was found that due to the extraordinary multiple intermolecular interactions involved in the ionic liquid units, one single sphere could differentially interact with broader classes of analytes, thus generating response patterns with remarkable diversity...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28986307/interleukin-1%C3%AE-and-tumor-necrosis-factor-%C3%AE-augment-acidosis-induced-rat-articular-chondrocyte-apoptosis-via-nuclear-factor-kappab-dependent-up-regulation-of-asic1a-channel
#10
Ren-Peng Zhou, Bei-Bei Dai, Ya-Ya Xie, Xiao-Shan Wu, Zhi-Sen Wang, Yue Li, Zhi-Qiang Wang, Sheng-Qin Zu, Jin-Fang Ge, Fei-Hu Chen
The acute-phase proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) demonstrate high-level expression and pleiotropic biological effects, and contribute to the progression and persistence of rheumatoid arthritis (RA). Acid hydrarthrosis is also an important pathological characteristic of RA, and the acid-sensing ion channel 1a (ASIC1a) plays a critical role in acidosis-induced chondrocyte cytotoxicity. However, the roles of IL-1β and TNF-α in acid-induced apoptosis of chondrocytes remain unclear...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28978442/mechanisms-responsible-for-%C3%AF-pore-currents-in-cav-calcium-channel-voltage-sensing-domains
#11
Stefania Monteleone, Andreas Lieb, Alexandra Pinggera, Giulia Negro, Julian E Fuchs, Florian Hofer, Jörg Striessnig, Petronel Tuluc, Klaus R Liedl
Mutations of positively charged amino acids in the S4 transmembrane segment of a voltage-gated ion channel form ion-conducting pathways through the voltage-sensing domain, named ω-current. Here, we used structure modeling and MD simulations to predict pathogenic ω-currents in CaV1.1 and CaV1.3 Ca(2+) channels bearing several S4 charge mutations. Our modeling predicts that mutations of CaV1.1-R1 (R528H/G, R897S) or CaV1.1-R2 (R900S, R1239H) linked to hypokalemic periodic paralysis type 1 and of CaV1.3-R3 (R990H) identified in aldosterone-producing adenomas conducts ω-currents in resting state, but not during voltage-sensing domain activation...
October 3, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28970722/pharmacological-evaluation-of-nsaid-induced-gastropathy-as-a-translatable-model-of-referred-visceral-hypersensitivity
#12
Michele Hummel, Terri Knappenberger, Meghan Reilly, Garth T Whiteside
AIM: To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. METHODS: Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice (n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated...
September 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28955292/molecular-mechanisms-that-contribute-to-bone-marrow-pain
#13
REVIEW
Jason J Ivanusic
Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28955199/endogenous-isoquinoline-alkaloids-agonists-of-acid-sensing-ion-channel-type-3
#14
Dmitry I Osmakov, Sergey G Koshelev, Yaroslav A Andreev, Sergey A Kozlov
Acid-sensing ion channels (ASICs) ASIC3 expressed mainly in peripheral sensory neurons play an important role in pain perception and inflammation development. In response to acidic stimuli, they can generate a unique biphasic current. At physiological pH 7.4, human ASIC3 isoform (hASIC3) is desensitized and able to generate only a sustained current. We found endogenous isoquinoline alkaloids (EIAs), which restore hASIC3 from desensitization and recover the transient component of the current. Similarly, rat ASIC3 isoform (rASIC3) can also be restored from desensitization (at pH < 7...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28954208/molecular-basis-of-dental-sensitivity-the-odontoblasts-are-multisensory-cells-and-express-multifunctional-ion-channels
#15
REVIEW
A Solé-Magdalena, M Martínez-Alonso, C A Coronado, L M Junquera, J Cobo, J A Vega
Odontoblasts are the dental pulp cells responsible for the formation of dentin. In addition, accumulating data strongly suggest that they can also function as sensory cells that mediate the early steps of mechanical, thermic, and chemical dental sensitivity. This assumption is based on the expression of different families of ion channels involved in various modalities of sensitivity and the release of putative neurotransmitters in response to odontoblast stimulation which are able to act on pulp sensory nerve fibers...
September 24, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/28949138/molecular-basis-for-allosteric-inhibition-of-acid-sensing-ion-channel-1a-by-ibuprofen
#16
Timothy Lynagh, José Luis Romero-Rojo, Camilla Lund, Stephan A Pless
A growing body of evidence links certain aspects of nonsteroidal anti-inflammatory drug (NSAID) pharmacology with acid-sensing ion channels (ASICs), a small family of excitatory neurotransmitter receptors implicated in pain and neuroinflammation. The molecular basis of NSAID inhibition of ASICs has remained unknown, hindering the exploration of this line of therapy. Here, we characterized the mechanism of inhibition, explored the molecular determinants of sensitivity, and sought to establish informative structure-activity relationships, using electrophysiology, site-directed mutagenesis, and voltage-clamp fluorometry...
September 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28928655/effects-of-simvastatin-beyond-dyslipidemia-exploring-its-antinociceptive-action-in-an-animal-model-of-complex-regional-pain-syndrome-type-i
#17
Graziela Vieira, Juliana Cavalli, Elaine C D Gonçalves, Tainara R Gonçalves, Larissa R Laurindo, Maíra Cola, Rafael C Dutra
Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28927426/the-acid-sensing-ion-channel-asic2-promotes-invasion-and-metastasis-of-colorectal-cancer-under-acidosis-by-activating-the-calcineurin-nfat1-axis
#18
Zhi-Hang Zhou, Jin-Wen Song, Wen Li, Xue Liu, Liu Cao, Lu-Ming Wan, Ying-Xia Tan, Shou-Ping Ji, Yu-Mei Liang, Feng Gong
BACKGROUND: The tumor acidic microenvironment, a common biochemical event in solid tumors, offers evolutional advantage for tumors cells and even enhances their aggressive phenotype. However, little is known about the molecular mechanism underlying the acidic microenvironment-induced invasion and metastasis. METHODS: We examined the expression of the acid-sending ion channel (ASIC) family members after acidic exposure using RT-PCR and immunofluoresence. Gene manipulation was applied to reveal the potential of ASIC2 on invasion, proliferation, colony formation of colorectal cancer (CRC)...
September 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28912013/acid-sensing-ion-channel-1-contributes-to-normal-olfactory-function
#19
Kiara T Vann, Zhi-Gang Xiong
Acid-sensing ion channels (ASICs) are cation channels activated by protons. ASIC1a, a primary ASIC subunit in the brain, was recently characterized in the olfactory bulb. The present study tested the hypothesis that ASIC1a is essential for normal olfactory function. Olfactory behavior of wild-type (WT) and ASIC1-/- mice was evaluated by using three standard olfactory tests: (1) the buried food test, (2) the olfactory habituation test, and (3) the olfactory preference test. In buried food test, ASIC1-/- mice had significantly longer latency to uncover buried food than WT mice...
January 30, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28906526/a-series-of-mg-zn-heterometallic-coordination-polymers-synthesis-characterization-and-fluorescence-sensing-for-fe-3-cs2-and-nitroaromatic-compounds
#20
Zhao-Feng Wu, Xiao-Ying Huang
Herein, the solvothermal preparations, crystal structures, and fluorescence properties of three Mg-Zn heterometallic coordination polymers (CPs), i.e. [Mg2Zn2(OH)2(1,4-NDC)3(H2O)2]·6H2O (1), [Mg1.13Zn1.87(1,4-NDC)3(dppe)(CH3OH)] (2), and [Mg1.17Zn1.83(1,4-NDC)3(py)2]·1.5py (3), based on the mixed ligands of 1,4-naphthalene dicarboxylic acid (1,4-H2NDC) and N-containing ligands of 1,3-di(4-pyridyl)propane (dppe) or pyridine (py) are presented. In the title compounds, Zn and Mg are statistically distributed, as confirmed by single crystal analysis, and the ratios of Zn and Mg have been identified by inductively coupled plasma (ICP) measurements...
September 26, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
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