scholarly journals Negative regulation of melatonin secretion by melatonin receptors in ovine pinealocytes

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255249
Author(s):  
Julie Lépinay ◽  
Catherine Taragnat ◽  
Jean-Philippe Dubois ◽  
Didier Chesneau ◽  
Ralf Jockers ◽  
...  
Keyword(s):  
Pineal Gland ◽  
Negative Regulation ◽  
G Protein Coupled Receptors ◽  
Melatonin Receptors ◽  
Camp Production ◽  
Melatonin Secretion ◽  
Adrenergic Agonist ◽  
Retinal Photoreceptors ◽  
First Time ◽  
G Protein Coupled

Melatonin (MLT) is a biological modulator of circadian and seasonal rhythms and reproduction. The photoperiodic information is detected by retinal photoreceptors and transmitted through nerve transmissions to the pineal gland, where MLT is synthesized and secreted at night into the blood. MLT interacts with two G protein-coupled receptors, MT1 and MT2. The aim of our work was to provide evidence for the presence of MLT receptors in the ovine pineal gland and define their involvement on melatonin secretion. For the first time, we identified the expression of MLT receptors with the specific 2-[125I]-MLT agonistic radioligand in ovin pinealocytes. The values of Kd and Bmax are 2.24 ± 1.1 nM and 20 ± 6.8 fmol/mg. MLT receptors are functional and inhibit cAMP production and activate ERK1/2 through pertussis toxin-sensitive Gi/o proteins. The MLT receptor antagonist/ inverse agonist luzindole increased cAMP production (189 ± 30%) and MLT secretion (866 ± 13%). The effect of luzindole on MLT secretion was additive with the effect of well-described activators of this pathway such as the β-adrenergic agonist isoproterenol and the α-adrenergic agonist phenylephrine. Co-incubation of all three compounds increased MLT secretion by 1236 ± 199%. These results suggest that MLT receptors are involved in the negative regulation of the synthesis of its own ligand in pinealocytes. While adrenergic receptors promote MLT secretion, MLT receptors mitigate this effect to limit the quantity of MLT secreted by the pineal gland.

Mapping the Heart

2010 ◽  
Vol 18 (4) ◽  
pp. 6-8
Author(s):  
Stephen W. Carmichael
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
G Protein Coupled Receptors ◽  
Receptor Subtypes ◽  
Cardiac Muscle Cells ◽  
Guanine Nucleotide Binding Protein ◽  
The Common ◽  
Guanine Nucleotide Binding ◽  
First Time ◽  
G Protein Coupled

Some of the receptors on the surface of cardiac muscle cells (cardiomyocytes) mediate the response of these cells to catecholamines by causing the production of the common second messenger cyclic adenosine monophosphate (cAMP). An example of such receptors are the β1- and β2-adrenergic receptors (βARs) that are heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Selective stimulation of these two receptor subtypes leads to distinct physiological and pathophysiological responses, but their precise location on the surface of cardiomyocytes has not been correlated with these responses. In an ingenious combination of techniques, Viacheslav Nikolaev, Alexey Moshkov, Alexander Lyon, Michele Miragoli, Pavel Novak, Helen Paur, Martin Lohse, Yuri Korchev, Sian Harding, and Julia Gorelik have mapped the function of these receptors for the first time.

scholarly journals Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Chao Gu ◽  
Yajing Chen ◽  
Yan Chen ◽  
Chun-Feng Liu ◽  
Zengyan Zhu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
G Protein ◽  
Metabotropic Glutamate Receptors ◽  
Microglial Activation ◽  
G Protein Coupled Receptors ◽  
Innate Immune ◽  
Melatonin Receptors ◽  
Immune Receptors ◽  
G Protein Coupled

Parkinson’s disease (PD) is one of the prevalent neurodegenerative diseases associated with preferential loss of dopaminergic (DA) neurons in the substantia nigra compacta (SNc) and accumulation of α-synuclein in DA neurons. Even though the precise pathogenesis of PD is not clear, a large number of studies have shown that microglia-mediated neuroinflammation plays a vital role in the process of PD development. G protein-coupled receptors (GPCRs) are widely expressed in microglia and several of them act as regulators of microglial activation upon corresponding ligands stimulations. Upon α-synuclein insults, microglia would become excessively activated through some innate immune receptors. Presently, as lack of ideal drugs for treating PD, certain GPCR which is highly expressed in microglia of PD brain and mediates neuroinflammation effectively could be a prospective source for PD therapeutic intervention. Here, six kinds of GPCRs and two types of innate immune receptors were introduced, containing adenosine receptors, purinergic receptors, metabotropic glutamate receptors, adrenergic receptors, cannabinoid receptors, and melatonin receptors and their roles in neuroinflammation; we highlighted the relationship between these six GPCRs and microglial activation in PD. Based on the existing findings, we tried to expound the implication of microglial GPCRs-regulated neuroinflammation to the pathophysiology of PD and their potential to become a new expectation for clinical therapeutics.

scholarly journals ASIC2b-dependent Regulation of ASIC3, an Essential Acid-sensing Ion Channel Subunit in Sensory Neurons via the Partner Protein PICK-1

2004 ◽  
Vol 279 (19) ◽  
pp. 19531-19539 ◽  
Author(s):  
Emmanuel Deval ◽  
Miguel Salinas ◽  
Anne Baron ◽  
Eric Lingueglia ◽  
Michel Lazdunski
Keyword(s):  
Ion Channel ◽  
Sensory Neurons ◽  
Ph Dependence ◽  
Pdz Domain ◽  
G Protein Coupled Receptors ◽  
Drg Neurons ◽  
Kinase C ◽  
C Terminus ◽  
First Time ◽  
G Protein Coupled

ASIC3, an acid-sensing ion channel subunit expressed essentially in sensory neurons, has been proposed to be involved in pain. We show here for the first time that native ASIC3-like currents were increased in cultured dorsal root ganglion (DRG) neurons following protein kinase C (PKC) stimulation. This increase was induced by the phorbol ester PDBu and by pain mediators, such as serotonin, which are known to activate the PKC pathway through their binding to G protein-coupled receptors. We demonstrate that this regulation involves the silent ASIC2b subunit, an ASIC subunit also expressed in sensory neurons. Indeed, heteromultimeric ASIC3/ASIC2b channels, but not homomeric ASIC3 channels, are positively regulated by PKC. The increase of ASIC3/ASIC2b current is accompanied by a shift in its pH dependence toward more physiological pH values and may lead to an increase of sensory neuron excitability. This regulation by PKC requires PICK-1 (protein interacting with C kinase), a PDZ domain-containing protein, which interacts with the ASIC2b C terminus.

scholarly journals Endosomal cAMP production broadly impacts the cellular phosphoproteome

2021 ◽  
Author(s):  
Nikoleta G. Tsvetanova ◽  
Michelle Trester-Zedlitz ◽  
Billy W. Newton ◽  
Grace E. Peng ◽  
Jeffrey R. Johnson ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Underlying Mechanism ◽  
G Protein Coupled Receptors ◽  
Camp Production ◽  
Unique Role ◽  
Endosomal Signaling ◽  
Functional Consequences ◽  
Phosphatase 2A ◽  
Cellular Responsiveness ◽  
G Protein Coupled

AbstractEndosomal signaling from G protein-coupled receptors (GPCRs) has emerged as a novel paradigm with important pharmacological and physiological implications. Yet, our knowledge of the functional consequences of activating intracellular GPCRs is incomplete. To address this gap, we combined an optogenetic approach for site-specific generation of the prototypical second messenger cyclic AMP (cAMP) with unbiased mass spectrometry-based analysis of phosphoproteomic effects. We identified 218 unique, high-confidence sites whose phosphorylation is either increased or decreased in response to cAMP production. We next determined that cAMP produced from endosomes led to more robust changes in phosphorylation than cAMP produced from the plasma membrane. Remarkably, this was true for the entire repertoire of identified targets, and irrespective of their annotated sub-cellular localization. Furthermore, we identified a particularly strong endosome bias for a subset of proteins that are dephosphorylated in response to cAMP. Through bioinformatics analysis, we established these targets as putative substrates for protein phosphatase 2A (PP2A), and we propose compartmentalized activation of PP2A-B56δ as the likely underlying mechanism. Altogether, our study extends the concept that endosomal signaling is a significant functional contributor to cellular responsiveness by establishing a unique role for localized cAMP production in defining categorically distinct phosphoresponses.

scholarly journals Lactate as an Astroglial Signal Augmenting Aerobic Glycolysis and Lipid Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Anemari Horvat ◽  
Robert Zorec ◽  
Nina Vardjan
Keyword(s):  
Lipid Metabolism ◽  
Brain Function ◽  
Lipid Droplets ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
G Protein Coupled Receptors ◽  
Camp Production ◽  
Signaling Mechanisms ◽  
G Protein Coupled ◽  
The Brain

Astrocytes, heterogeneous neuroglial cells, contribute to metabolic homeostasis in the brain by providing energy substrates to neurons. In contrast to predominantly oxidative neurons, astrocytes are considered primarily as glycolytic cells. They take up glucose from the circulation and in the process of aerobic glycolysis (despite the normal oxygen levels) produce L-lactate, which is then released into the extracellular space via lactate transporters and possibly channels. Astroglial L-lactate can enter neurons, where it is used as a metabolic substrate, or exit the brain via the circulation. Recently, L-lactate has also been considered to be a signaling molecule in the brain, but the mechanisms of L-lactate signaling and how it contributes to the brain function remain to be fully elucidated. Here, we provide an overview of L-lactate signaling mechanisms in the brain and present novel insights into the mechanisms of L-lactate signaling via G-protein coupled receptors (GPCRs) with the focus on astrocytes. We discuss how increased extracellular L-lactate upregulates cAMP production in astrocytes, most likely viaL-lactate-sensitive Gs-protein coupled GPCRs. This activates aerobic glycolysis, enhancing L-lactate production and accumulation of lipid droplets, suggesting that L-lactate augments its own production in astrocytes (i.e., metabolic excitability) to provide more L-lactate for neurons and that astrocytes in conditions of increased extracellular L-lactate switch to lipid metabolism.

scholarly journals Receptor-activity-modifying protein 1 forms heterodimers with two G-protein-coupled receptors to define ligand recognition

2000 ◽  
Vol 351 (2) ◽  
pp. 347-351 ◽  
Author(s):  
Kerstin LEUTHÄUSER ◽  
Remo GUJER ◽  
Amaya ALDECOA ◽  
R. ANNE McKINNEY ◽  
Roman MUFF ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Receptor Activity ◽  
Cross Linking ◽  
Human Calcitonin ◽  
Camp Production ◽  
Surface Complexes ◽  
Receptor Activity Modifying Proteins ◽  
G Protein Coupled

Receptor-activity-modifying proteins (RAMPs) with single transmembrane domains define the function of two G-protein-coupled receptors of the B family. Cell-surface complexes of human RAMP1 (hRAMP1) and human calcitonin (CT) receptor isotype 2 (hCTR2) or rat CT-receptor-like receptor (rCRLR) have now been identified through protein cross-linking, co-immunoprecipitation and confocal microscopy. They are two distinct CT-gene-related peptide (CGRP) receptors coupled to cAMP production and pharmacologically distinguished by the CT and CGRP antagonists salmon CT(8-32) and human or rat CGRP(8-37). Thus direct molecular interactions of hRAMP1 with hCTR2 or rCRLR are required for CGRP recognition. hCTR2, moreover, adopts non-traditional functions through its association with hRAMP1.

Effect of melatonin implants on reproductive performance in ewes

1988 ◽  
Vol 1988 ◽  
pp. 51-51
Author(s):  
W. Haresign ◽  
A.R. Peters ◽  
G.M. Webster ◽  
J.W.B. King ◽  
L.D. Staples
Keyword(s):  
Pineal Gland ◽  
Breeding Season ◽  
Reproductive Performance ◽  
Present Experiment ◽  
Reproductive Activity ◽  
Breeding Cycle ◽  
Melatonin Secretion ◽  
Neural Signal ◽  
Retinal Photoreceptors ◽  
Subcutaneous Implant

It has been known for many years that the annual breeding cycle of the sheep is controlled by photoperiod. More recently it has become apparent that this process involves the pineal gland. Light is effectively monitored by retinal photoreceptors within the eye which transmit a neural signal to the pineal gland, and this in turn responds by secreting melatonin during the period of darkness. As daylength decreases in the autumn, the duration of elevated melatonin secretion increases, and this changing ratio of high:low melatonin during each 24h period stimulates breeding activity.Both timed (by afternoon feeding or injection) and continuous (by subcutaneous or vaginal implant) administration of exogenous melatonin to ewes in mid-summer have recently been shown to mimic the effects of decreasing photoperiod by advancing the onset of the breeding season. The present experiment was undertaken to investigate the ability of a subcutaneous implant of melatonin to manipulate reproductive activity of ewes under field conditions in the U.K.

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