scholarly journals Lactate activates hypothalamic POMC neurons by intercellular signaling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
P. Órdenes ◽  
P. S. Villar ◽  
E. Tarifeño-Saldivia ◽  
M. Salgado ◽  
R. Elizondo-Vega ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Pertussis Toxin ◽  
Intercellular Communication ◽  
Hydroxybenzoic Acid ◽  
Intercellular Signaling ◽  
Genetic Approach ◽  
Acid Receptor ◽  
Hydroxycarboxylic Acid ◽  
Lactate Transporter ◽  
Intracellular Action

AbstractPrevious studies indicate that the activity of hypothalamic POMC neurons can be regulated by glucose via intracellular mechanisms, but its regulation by lactate is poorly understood. In addition to its energetic role, lactate acts as a signaling molecule. In this study, we evaluated the function and location of the lactate receptor, hydroxycarboxylic acid receptor 1 (HCAR1). We used a conditional genetic approach to label POMC neurons and evaluated their sensitivity to lactate using patch-clamp recordings. l-Lactate and 3-chloro-5-hydroxybenzoic acid (3Cl-HBA), HCAR1 specific agonist depolarized POMC neurons and the increase in excitability was abolished by pertussis toxin (PTX), indicating the involvement of Gαi/o-protein-coupled receptors. In addition, the depolarization of a subset of POMC neurons was sensitive to α-cyano-4-hydroxycinnamate (4-CIN), a lactate transporter blocker, suggesting that the depolarization induced by l-lactate can also occur by direct intracellular action. Surprisingly, HCAR1 was not detected in POMC neurons, but instead localized in astrocytes. These results suggest a new lactate-mediated mechanism for astrocyte-neuron intercellular communication.

scholarly journals Bystander Attenuation of Neuronal and Astrocyte Intercellular Communication by Murine Cytomegalovirus Infection of Glia

2007 ◽  
Vol 81 (13) ◽  
pp. 7286-7292 ◽  
Author(s):  
Winson S. C. Ho ◽  
Anthony N. van den Pol
Keyword(s):  
Intercellular Communication ◽  
Neuronal Development ◽  
Primary Cultures ◽  
Synaptic Activity ◽  
Murine Cytomegalovirus ◽  
Intercellular Signaling ◽  
Mcmv Infection ◽  
High Potassium ◽  
Infected Cells ◽  
The Brain

ABSTRACT Astrocytes are the first cells infected by murine cytomegalovirus (MCMV) in primary cultures of brain. These cells play key roles in intercellular signaling and neuronal development, and they modulate synaptic activity within the nervous system. Using ratiometric fura-2 digital calcium imaging of >8,000 neurons and glia, we found that MCMV-infected astrocytes showed an increase in intracellular basal calcium levels and an enhanced response to neuroactive substances, including glutamate and ATP, and to high potassium levels. Cultured neurons with no sign of MCMV infection showed attenuated synaptic signaling after infection of the underlying astrocyte substrate, and intercellular communication between astrocytes with no sign of infection was reduced by the presence of infected glia. These bystander effects would tend to cause further deterioration of cellular communication in the brain in addition to the problems caused by the loss of directly infected cells.

scholarly journals Non-Coding RNAs in Breast Cancer: Intracellular and Intercellular Communication

2018 ◽  
Vol 4 (4) ◽  
pp. 40 ◽  
Author(s):  
Carolyn Klinge
Keyword(s):  
Breast Cancer ◽  
Intercellular Communication ◽  
Intracellular Signaling ◽  
Colorectal Neoplasia ◽  
Breast Tumors ◽  
Estrogen Receptor Α ◽  
Circular Rnas ◽  
Intercellular Signaling ◽  
Protein Coding ◽  
Non Coding Rnas

Non-coding RNAs (ncRNAs) are regulators of intracellular and intercellular signaling in breast cancer. ncRNAs modulate intracellular signaling to control diverse cellular processes, including levels and activity of estrogen receptor α (ERα), proliferation, invasion, migration, apoptosis, and stemness. In addition, ncRNAs can be packaged into exosomes to provide intercellular communication by the transmission of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) to cells locally or systemically. This review provides an overview of the biogenesis and roles of ncRNAs: small nucleolar RNA (snRNA), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), miRNAs, and lncRNAs in breast cancer. Since more is known about the miRNAs and lncRNAs that are expressed in breast tumors, their established targets as oncogenic drivers and tumor suppressors will be reviewed. The focus is on miRNAs and lncRNAs identified in breast tumors, since a number of ncRNAs identified in breast cancer cells are not dysregulated in breast tumors. The identity and putative function of selected lncRNAs increased: nuclear paraspeckle assembly transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), steroid receptor RNA activator 1 (SRA1), colon cancer associated transcript 2 (CCAT2), colorectal neoplasia differentially expressed (CRNDE), myocardial infarction associated transcript (MIAT), and long intergenic non-protein coding RNA, Regulator of Reprogramming (LINC-ROR); and decreased levels of maternally-expressed 3 (MEG3) in breast tumors have been observed as well. miRNAs and lncRNAs are considered targets of therapeutic intervention in breast cancer, but further work is needed to bring the promise of regulating their activities to clinical use.

scholarly journals Natural biased signaling of hydroxycarboxylic acid receptor 3 and G protein-coupled receptor 84

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Anna Peters ◽  
Philipp Rabe ◽  
Petra Krumbholz ◽  
Hermann Kalwa ◽  
Robert Kraft ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Acid Receptor ◽  
Hydroxycarboxylic Acid ◽  
Biased Signaling ◽  
G Protein Coupled

Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2

Metabolism ◽  
2016 ◽  
Vol 65 (2) ◽  
pp. 102-113 ◽  
Author(s):  
Emily C. Graff ◽  
Han Fang ◽  
Desiree Wanders ◽  
Robert L. Judd
Keyword(s):  
Acid Receptor ◽  
Hydroxycarboxylic Acid ◽  
Anti Inflammatory

Tranexamic Acid Impairs γ-Aminobutyric Acid Receptor Type A–mediated Synaptic Transmission in the Murine Amygdala

2014 ◽  
Vol 120 (3) ◽  
pp. 639-649 ◽  
Author(s):  
Stephan Kratzer ◽  
Hedwig Irl ◽  
Corinna Mattusch ◽  
Martina Bürge ◽  
Jörg Kurz ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Synaptic Transmission ◽  
Tranexamic Acid ◽  
Gabaa Receptor ◽  
Type A ◽  
Aminobutyric Acid ◽  
Receptor Type ◽  
Voltage Sensitive Dye ◽  
Acid Receptor ◽  
Neuronal Excitation

Abstract Background: Tranexamic acid (TXA) is commonly used to reduce blood loss in cardiac surgery and in trauma patients. High-dose application of TXA is associated with an increased risk of postoperative seizures. The neuronal mechanisms underlying this proconvulsant action of TXA are not fully understood. In this study, the authors investigated the effects of TXA on neuronal excitability and synaptic transmission in the basolateral amygdala. Methods: Patch clamp recordings and voltage-sensitive dye imaging were performed in acute murine brain slices. Currents through N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and γ-aminobutyric acid receptor type A (GABAA) receptors were recorded. GABAA receptor–mediated currents were evoked upon electrical stimulation or upon photolysis of caged GABA. TXA was applied at different concentrations. Results: Voltage-sensitive dye imaging demonstrates that TXA (1 mM) reversibly enhances propagation of neuronal excitation (mean ± SEM, 129 ± 6% of control; n = 5). TXA at concentrations of 0.1, 0.3, 1, 5, or 10 mM led to a dose-dependent reduction of GABAA receptor–mediated currents in patch clamp recordings. There was no difference in the half-maximal inhibitory concentration for electrically (0.76 mM) and photolytically (0.84 mM) evoked currents (n = 5 to 9 for each concentration), and TXA did not affect the paired-pulse ratio of GABAA receptor–mediated currents. TXA did not impact glutamatergic synaptic transmission. Conclusions: This study clearly demonstrates that TXA enhances neuronal excitation by antagonizing inhibitory GABAergic neurotransmission. The results provide evidence that this effect is mediated via postsynaptic mechanisms. Because GABAA receptor antagonists are known to promote epileptiform activity, this effect might explain the proconvulsant action of TXA.

scholarly journals The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1: Expression and action in brain

2015 ◽  
Vol 93 (7) ◽  
pp. 1045-1055 ◽  
Author(s):  
Cecilie Morland ◽  
Knut Husø Lauritzen ◽  
Maja Puchades ◽  
Signe Holm-Hansen ◽  
Krister Andersson ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Acid Receptor ◽  
Hydroxycarboxylic Acid ◽  
G Protein Coupled
Sign in / Sign up

Export Citation Format

Share Document