NAADP as an intracellular messenger regulating lysosomal calcium-release channels

2010 ◽  
Vol 38 (6) ◽  
pp. 1424-1431 ◽  
Author(s):  
Antony Galione ◽  
Anthony J. Morgan ◽  
Abdelilah Arredouani ◽  
Lianne C. Davis ◽  
Katja Rietdorf ◽  
...  
Keyword(s):  
Calcium Release ◽  
Mechanisms Of Action ◽  
Endocytic Pathway ◽  
The Novel ◽  
Major Site ◽  
Calcium Release Channels ◽  
Biochemical Studies ◽  
Site Of Action ◽  
Intracellular Messenger

Recent studies into the mechanisms of action of the Ca2+-mobilizing messenger NAADP (nicotinic acid–adenine dinucleotide phosphate) have demonstrated that a novel family of intracellular Ca2+-release channels termed TPCs (two-pore channels) are components of the NAADP receptor. TPCs appear to be exclusively localized to the endolysosomal system. These findings confirm previous pharmacological and biochemical studies suggesting that NAADP targets acidic Ca2+ stores rather than the endoplasmic reticulum, the major site of action of the other two principal Ca2+-mobilizing messengers, InsP3 and cADPR (cADP-ribose). Studies of the messenger roles of NAADP and the function of TPCs highlight the novel role of lysosomes and other organelles of the endocytic pathway as messenger-regulated Ca2+ stores which also affects the regulation of the endolysosomal system.

scholarly journals Phosphorylation-Dependent Regulation of Ryanodine Receptors

2001 ◽  
Vol 153 (4) ◽  
pp. 699-708 ◽  
Author(s):  
Steven O. Marx ◽  
Steven Reiken ◽  
Yuji Hisamatsu ◽  
Marta Gaburjakova ◽  
Jana Gaburjakova ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Rapid Identification ◽  
Calcium Release Channels ◽  
Macromolecular Complexes ◽  
Protein Binding Sites ◽  
Skeletal Muscle Contraction

Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function.

scholarly journals Critical Role of Intracellular RyR1 Calcium Release Channels in Skeletal Muscle Function and Disease

2016 ◽  
Vol 6 ◽  
Author(s):  
Erick O. Hernández-Ochoa ◽  
Stephen J. P. Pratt ◽  
Richard M. Lovering ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Calcium Release ◽  
Critical Role ◽  
Skeletal Muscle Function ◽  
Calcium Release Channels

Differential effects of methylmercuric chloride and mercuric chloride on the L-glutamate and potassium evoked release of [3H]dopamine from mouse striatal slices

1986 ◽  
Vol 64 (5) ◽  
pp. 656-660 ◽  
Author(s):  
S. J. McKay ◽  
J. N. Reynolds ◽  
W. J. Racz
Keyword(s):  
Calcium Channel ◽  
Glutamate Receptor ◽  
Mercuric Chloride ◽  
Neurotransmitter Release ◽  
Mechanisms Of Action ◽  
Major Site ◽  
Striatal Slices ◽  
Differential Effects ◽  
Methylmercuric Chloride ◽  
Site Of Action

The effects of CH3HgCl and HgCl2 on the evoked release of 3H from mouse striatal slices prelabelled with [3H]dopamine have been examined. CH3HgCl (10 μM) was observed to increase the L-glutamate-evoked release of [3H]dopamine, while HgCl2 (10 μM) had no effect. In contrast, CH3HgCl at concentrations up to 100 μM had no effect on the 25 mM K+-stimulated release of [3H]dopamine, whereas HgCl2 (100 μM) significantly reduced the 25 mM K+-stimulated release of [3H]dopamine. Thus CH3HgCl and HgCl2 have differential effects on the L-glutamate- and K+-stimulated release of [3H]dopamine from mouse striatal slices, suggesting that these compounds may have different sites and (or) mechanisms of action in altering neurotransmitter release. It is suggested that CH3HgCl may act predominantly at intracellular sites or at the level of the L-glutamate receptor, whereas the major site of action of HgCl2 may be the voltage-operated calcium channel.

scholarly journals THE ROLE OF IMMUNITY IN THE PATHOGENESIS OF EXPERIMENTAL RETROGRADE PYELONEPHRITIS

1964 ◽  
Vol 119 (6) ◽  
pp. 869-879 ◽  
Author(s):  
Betty W. Hunter ◽  
Lona L. Akins ◽  
Jay P. Sanford
Keyword(s):  
Protective Effect ◽  
Bacterial Growth ◽  
Proteus Mirabilis ◽  
Major Site ◽  
Site Of Action ◽  
Intravesical Injection ◽  
Prior Infection

Retrograde pyelonephritis was produced in rats by the intravesical injection of Proteus mirabilis. When animals were preimmunized against Proteus mirabilis by (a) prior infection, (b) administration of antigen, or (c) passively transferred antiserum, they were resistant to infection by proteus when challenged by the retrograde route. The protective effect of specific preimmunization in retrograde pyelonephritis indicates that a major site of action is retardation of bacterial growth within the parenchyma of the kidney.

Recognizing the role of CGRP and CGRP receptors in migraine and its treatment

Cephalalgia ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 366-373 ◽  
Author(s):  
Lars Edvinsson ◽  
Karin Warfvinge
Keyword(s):  
Small Molecules ◽  
Migraine Headache ◽  
The Novel ◽  
Trigeminovascular System ◽  
Calcitonin Gene ◽  
Site Of Action ◽  
Acute Attacks ◽  
Sensory Nervous System ◽  
The Brain

Premise The brain and the sensory nervous system contain a rich supply of calcitonin gene-related peptide (CGRP) and CGRP receptor components. Clinical studies have demonstrated a correlation between CGRP release and acute migraine headache that led to the development of CGRP-specific drugs that either abort acute attacks of migraine (gepants) or are effective as prophylaxis (antibodies). However, there is still much discussion concerning the site of action of these drugs. Problem Here we describe the most recent data related to CGRP in the trigeminal ganglion and its connections to the CNS, putative key regions involved in migraine pathophysiology. Gepants are small molecules that have limited ability to cross the blood-brain barrier (BBB), whereas CGRP antibodies are 1500 times larger molecules, and are virtually excluded from the brain, with a BBB permeability of < 0.1%. Thus we propose that the primary site of action for the antimigraine drugs is outside the CNS in areas not limited by the BBB. Potential solution Therefore, it is reasonable to discuss the localization of CGRP and its receptor components in relation to the BBB. The trigeminovascular system, located outside the BBB, has a key role in migraine symptomatology, and it is likely targeted by the novel CGRP drugs that successfully terminate migraine headache.

ROLE OF THE NOVEL INTRODUCED PAN-INTESTINAL CAPSULE ENDOSCOPY SYSTEM IN CELIAC DISEASE

2019 ◽  
Author(s):  
F Foerster ◽  
K Mönkemüller ◽  
PR Galle ◽  
H Neumann
Keyword(s):  
Celiac Disease ◽  
Capsule Endoscopy ◽  
The Novel

Low melatonin as a contributor to SARS-CoV-2 disease

2020 ◽  
Vol 3 (4) ◽  
pp. 558-576
Author(s):  
Seithikurippu R Pandi-Perumal ◽  
Daniel P Cardinali ◽  
Russel J Reiter ◽  
Gregory M Brown
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Phosphorylation ◽  
Pineal Gland ◽  
Oxygen Species ◽  
Cytokine Storm ◽  
Major Site ◽  
Immune Modulator ◽  
Inflammatory Agent ◽  
Site Of Action ◽  
Extrapineal Melatonin

That the pineal gland is a source of melatonin is widely known; however, by comparison, few know of the much larger pool of extrapineal melatonin. That pool is widely distributed in all animals, including those that do not have a pineal gland, e.g., insects.  Extrapineal melatonin is not released into the blood but is used locally to function as an antioxidant, anti-inflammatory agent, etc. A major site of action of peripherally-produced melatonin is the mitochondria where it neutralizes reactive oxygen species (ROS) that are generated during oxidative phosphorylation. Its role also includes major actions as an immune modulator reducing overreactions to foreign agents while simultaneously boosting immune processes. During a pandemic such as coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, melatonin is capable of suppressing the damage inflicted by the cytokine storm. The implications of melatonin in susceptibility and treatment of COVID-19 disease are discussed. 

Patterns: Rosamond Lehmann

2018 ◽  
Author(s):  
Vike Martina Plock
Keyword(s):  
Coming Of Age ◽  
Public Image ◽  
Market Forces ◽  
The Novel ◽  
Fashion Industry ◽  
To The Lighthouse ◽  
Fashion Magazines ◽  
Female Authorship ◽  
Rosamond Lehmann

This chapter analyzes the role of fashion as a discursive force in Rosamond Lehmann’s 1932 coming-of-age novel Invitation to the Waltz. Reading the novel alongside such fashion magazines as Vogue, it demonstrates Lehmann’s awareness that 1920s fashion, in spite of its carefully stylized public image as harbinger of originality, emphasized the importance of following preconceived (dress) patterns in the successful construction of modern feminine types. Invitation to the Waltz, it argues, opposes the production of patterned types and celebrates difference and disobedience in its stead. At the same time, the novel’s formal appearance is nonetheless dependent on the very same tenets it criticizes. On closer scrutiny, it is seen to reveal its resemblance to Virginia Woolf’s To the Lighthouse (1927). A tension between imitation and originality determines sartorial fashion choices. This chapter shows that female authorship in the inter-war period was subjected to the same market forces that controlled and sustained the organization of the fashion industry.

THYROID STIMULATORS AND THYROID STIMULATION

1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke
Keyword(s):  
Regulatory System ◽  
Control Site ◽  
Thyroid Cell ◽  
Primary Control ◽  
Physico Chemical ◽  
Site Of Action ◽  
Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

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