Molecular and functional characterization of the mouse intracardiac nervous system

Background: The intracardiac nervous system (ICNS) refers to clusters of neurons, located within the heart, that participate to the neuronal regulation of cardiac functions and are involved in the initiation of cardiac arrhythmias. Therefore, deciphering the role of the ICNS in cardiac physiology and physiopathology is mandatory. Whereas transgenic mouse models represent powerful tools to reach this goal, the mouse ICNS is still poorly characterized. Objective: The objective of the present study was to provide a phenotypic, electrophysiological and pharmacological characterization of the mouse ICNS. Methods: Global cardiac innervation and phenotypic diversity was investigated by performing immunohistochemistry on cleared murine heart and on tissue sections. Patch clamp technique was used for electrophysiological and pharmacological characterization of isolated mouse intracardiac neurons. Results: We identified the expression of 7 distinct neuronal markers within mouse intracardiac neurons demonstrating the neurochemical diversity of this network. Of note, we described for the first time in mouse, the existence of neuron expressing the calcium binding protein calbindin, the neuropeptide Y (NPY) and the cocain and amphetamine regulated transcript (CART) peptide. Electrophysiological studies also revealed the existence of two different neuronal population based on their electrical behavior. Finally, we demonstrated that these neurons can be modulated by several neuromodulators. Conclusion: This study demonstrated that mouse ICNS shares similar molecular and functional complexity to that of other species and therefore is a suitable model to decipher the role of individual neuronal subtypes in the modulation of cardiac function and in the initiation of cardiac arrhythmias.

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Acid-Sensing Ion Channels

The Oxford Handbook of Neuronal Ion Channels ◽

10.1093/oxfordhb/9780190669164.013.12 ◽

2020 ◽

Author(s):

Stefan Gründer

Keyword(s):

Nervous System ◽

Ion Channels ◽

Excitatory Synapses ◽

Detailed Characterization ◽

High Affinity ◽

Acid Sensing Ion Channels ◽

Long Time ◽

Pathological Pain

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. Being almost ubiquitously present in neurons of the vertebrate nervous system, their precise function remained obscure for a long time. Various animal toxins that bind to ASICs with high affinity and specificity have been tremendously helpful in uncovering the role of ASICs. We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. Moreover, detailed characterization of mouse models uncovered an unanticipated role of ASICs in disorders of the nervous system like stroke, multiple sclerosis, and pathological pain. This review provides an overview on the expression, structure, and pharmacology of ASICs plus a summary of what is known and what is still unknown about their physiological functions and their roles in diseases.

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Insertion Hot Spots of DIRS1 Retrotransposon and Chromosomal Diversifications among the Antarctic Teleosts Nototheniidae

International Journal of Molecular Sciences ◽

10.3390/ijms20030701 ◽

2019 ◽

Vol 20 (3) ◽

pp. 701 ◽

Cited By ~ 3

Author(s):

Juliette Auvinet ◽

Paula Graça ◽

Laura Ghigliotti ◽

Eva Pisano ◽

Agnès Dettaï ◽

...

Keyword(s):

Hot Spots ◽

Chromosomal Rearrangements ◽

Antarctic Fish ◽

Wide Distribution ◽

Suitable Model ◽

Fish Family ◽

The Antarctic ◽

Antarctic Teleosts

By their faculty to transpose, transposable elements are known to play a key role in eukaryote genomes, impacting both their structuration and remodeling. Their integration in targeted sites may lead to recombination mechanisms involved in chromosomal rearrangements. The Antarctic fish family Nototheniidae went through several waves of species radiations. It is a suitable model to study transposable element (TE)-mediated mechanisms associated to genome and chromosomal diversifications. After the characterization of Gypsy (GyNoto), Copia (CoNoto), and DIRS1 (YNoto) retrotransposons in the genomes of Nototheniidae (diversity, distribution, conservation), we focused on their chromosome location with an emphasis on the three identified nototheniid radiations (the Trematomus, the plunderfishes, and the icefishes). The strong intrafamily TE conservation and wide distribution across species of the whole family suggest an ancestral acquisition with potential secondary losses in some lineages. GyNoto and CoNoto (including Hydra and GalEa clades) mostly produced interspersed signals along chromosomal arms. On the contrary, insertion hot spots accumulating in localized regions (mainly next to centromeric and pericentromeric regions) highlighted the potential role of YNoto in chromosomal diversifications as facilitator of the fusions which occurred in many nototheniid lineages, but not of the fissions.

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Pharmacological Characterization of Sephadex-lnduced Oedema in Rat Paws: Predominant Role of Serotonin and Platelet-Activating Factor

International Archives of Allergy and Immunology ◽

10.1159/000237269 ◽

1996 ◽

Vol 109 (4) ◽

pp. 398-406 ◽

Cited By ~ 7

Author(s):

Janetti N. Francischi ◽

Murilo F. Dias ◽

Orivaldo A. Rocha ◽

Maria S. de Abreu Castro ◽

Maria A. Kiyomi Funayama Tatsuo ◽

...

Keyword(s):

Platelet Activating Factor ◽

Predominant Role ◽

Pharmacological Characterization

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Pharmacological Characterization of an Adenylyl Cyclase-Coupled 5-HT Receptor in Aplysia: Comparison With Mammalian 5-HT Receptors

Journal of Neurophysiology ◽

10.1152/jn.01004.2002 ◽

2003 ◽

Vol 89 (3) ◽

pp. 1440-1455 ◽

Cited By ~ 22

Author(s):

Jonathan E. Cohen ◽

Chiadi U. Onyike ◽

Virginia L. McElroy ◽

Allison H. Lin ◽

Thomas W. Abrams

Keyword(s):

Adenylyl Cyclase ◽

Rank Order ◽

Physiological Saline ◽

Receptor Subtypes ◽

Pharmacological Profile ◽

Pharmacological Characterization ◽

Firing Properties ◽

Stimulation Of

We attempted to identify compounds that are effective in blocking the serotonin (5-hydroxytryptamine, 5-HT) receptor(s) that activate adenylyl cyclase (AC) in Aplysia CNS. We call this class of receptor 5-HTapAC. Eight of the 14 antagonists tested were effective against 5-HTapAC in CNS membranes with the following rank order of potency: methiothepin > metergoline ∼ fluphenazine > clozapine > cyproheptadine ∼ risperidone ∼ ritanserin > NAN-190. GR-113808, olanzapine, Ro-04-6790, RS-102221, SB-204070, and spiperone were inactive. Methiothepin completely blocked 5-HT stimulation of AC with a K b of 18 nM. Comparison of the pharmacological profile of the 5-HTapAC receptor with those of mammalian 5-HT receptor subtypes suggested it most closely resembles the 5-HT6 receptor. AC stimulation in Aplysia sensory neuron (SN) membranes was also blocked by methiothepin. Methiothepin substantially inhibited two effects of 5-HT on SN firing properties that are mediated by a cAMP-dependent reduction in S-K+ current: spike broadening in tetraethylammonium/nifedipine and increased excitability. Consistent with cyproheptadine blocking 5-HT stimulation of AC, cyproheptadine also blocked the 5-HT-induced increase in SN excitability. Methiothepin was less effective in blocking AC-mediated modulatory effects of 5-HT in electrophysiological experiments on SNs than in blocking AC stimulation in CNS or SN membranes. This reduction in potency appears to be due to effects of the high ionic strength of physiological saline on the binding of this antagonist to the receptor. Methiothepin also antagonized AC-coupled dopamine receptors but not AC-coupled small cardioactive peptide receptors. In conjunction with other pharmacological probes, this antagonist should be useful in analyzing the role of 5-HT in various forms of neuromodulation in Aplysia.

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The role of the autonomic nervous system in cardiac arrhythmias: The neuro-cardiac axis, more foe than friend?

Trends in Cardiovascular Medicine ◽

10.1016/j.tcm.2020.04.011 ◽

2020 ◽

Author(s):

Antonis A. Manolis ◽

Theodora A. Manolis ◽

Evdoxia J. Apostolopoulos ◽

Naomi E. Apostolaki ◽

Helen Melita ◽

...

Keyword(s):

Nervous System ◽

Autonomic Nervous System ◽

Cardiac Arrhythmias ◽

Autonomic Nervous

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Anxiogenic and Stressor Effects of the Hypothalamic Neuropeptide RFRP-3 Are Overcome by the NPFFR Antagonist GJ14

Endocrinology ◽

10.1210/en.2015-1532 ◽

2015 ◽

Vol 156 (11) ◽

pp. 4152-4162 ◽

Cited By ~ 30

Author(s):

Joon S. Kim ◽

Phil W. Brownjohn ◽

Blake S. Dyer ◽

Massimiliano Beltramo ◽

Christopher S. Walker ◽

...

Keyword(s):

Hpa Axis ◽

Stimulatory Action ◽

Pharmacological Characterization ◽

Neuropeptide Ff ◽

Chronic Infusion ◽

Corticosterone Release

RFamide-related peptide-3 (RFRP-3) is a recently discovered neuropeptide that has been proposed to play a role in the stress response. We aimed to elucidate the role of RFRP-3 and its receptor, neuropeptide FF (NPFF1R), in modulation of stress and anxiety responses. To achieve this, we characterized a new NPFF1R antagonist because our results showed that the only commercially available putative antagonist, RF9, is in fact an agonist at both NPFF1R and the kisspeptin receptor (KISS1R). We report here the identification and pharmacological characterization of GJ14, a true NPFFR antagonist. In in vivo tests of hypothalamic-pituitary-adrenal (HPA) axis function, GJ14 completely blocked RFRP-3-induced corticosterone release and neuronal activation in CRH neurons. Furthermore, chronic infusion of GJ14 led to anxiolytic-like behavior, whereas RFRP-3 infusion had anxiogenic effects. Mice receiving chronic RFRP-3 infusion also had higher basal circulating corticosterone levels. These results indicate a stimulatory action of RFRP-3 on the HPA axis, consistent with the dense expression of NPFF1R in the vicinity of CRH neurons. Importantly, coinfusion of RFRP-3 and GJ14 completely reversed the anxiogenic and HPA axis-stimulatory effects of RFRP-3. Here we have established the role of RFRP-3 as a regulator of stress and anxiety. We also show that GJ14 can reverse the effects of RFRP-3 both in vitro and in vivo. Infusion of GJ14 causes anxiolysis, revealing a novel potential target for treating anxiety disorders.

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Pharmacological Characterization of [3H]ATPCA as a Substrate for Studying the Functional Role of the Betaine/GABA Transporter 1 and the Creatine Transporter

ACS Chemical Neuroscience ◽

10.1021/acschemneuro.7b00351 ◽

2017 ◽

Vol 9 (3) ◽

pp. 545-554 ◽

Cited By ~ 5

Author(s):

Anas Al-Khawaja ◽

Anne S. Haugaard ◽

Ales Marek ◽

Rebekka Löffler ◽

Louise Thiesen ◽

...

Keyword(s):

Functional Role ◽

Gaba Transporter ◽

Pharmacological Characterization ◽

Creatine Transporter ◽

Gaba Transporter 1

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Minireview: The Adipocyte—At the Crossroads of Energy Homeostasis, Inflammation, and Atherosclerosis

Endocrinology ◽

10.1210/en.2003-0580 ◽

2003 ◽

Vol 144 (9) ◽

pp. 3765-3773 ◽

Cited By ~ 771

Author(s):

Michael W. Rajala ◽

Philipp E. Scherer

Keyword(s):

Adipose Tissue ◽

Energy Homeostasis ◽

Secretory Proteins ◽

Pharmacological Characterization ◽

Endocrine Organ ◽

Insulin Resistant ◽

Artery Disease ◽

Caloric Excess

Abstract Adipose tissue evolved to efficiently store energy for times of caloric restriction. The large caloric excess common in many Western diets has negated the need for this thrifty function, leaving adipose tissue ill-equipped to handle this increased load. An excess of adipose tissue increases risk for a number of conditions including coronary artery disease, hypertension, dyslipidemias, type 2 diabetes, and even cancer. Indeed, the ability of the adipocyte to function properly when engorged with lipid can lead to lipid accumulation in other tissues, reducing their ability to function and respond normally. The role of adipose tissue as an endocrine organ capable of secreting a number of adipose tissue-specific or enriched hormones, known as adipokines, is gaining appreciation. The normal balance of these adipose tissue secretory proteins is perturbed in obesity. Paradoxically, the lack of normal adipose tissue, as seen in cases of lipodystrophy and lipoatrophy, is also associated with pathologic sequelae similar to what is seen with obesity. The pathologic findings associated with lack of adipose tissue, largely due to inability to properly store lipids, may also be due to a lack of adipokines. In this review, we highlight the role of adipose tissue as an endocrine organ focusing on some of the recent advances in the identification and pharmacological characterization of adipokines as well as their regulation in the context of obesity and insulin-resistant states.

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