scholarly journals Functional characterization of the biogenic amine transporter system on human macrophages

2021 ◽  
Author(s):  
Phillip M Mackie ◽  
Adithya Gopinath ◽  
Dominic M Montas ◽  
Alyssa Nielsen ◽  
Rachel Nolan ◽  
...  
Keyword(s):  
Biogenic Amine ◽  
Functional Characterization ◽  
Human Monocyte ◽  
Paracrine Signaling ◽  
Macrophage Response ◽  
Reverse Transport ◽  
The Central Nervous System ◽  
Health And Disease

AbstractMonocyte-derived macrophages are key players in tissue homeostasis and disease regulated by a variety of signaling molecules. Recent literature has highlighted the ability for biogenic amines to regulate macrophage functions, but the mechanisms governing biogenic amine signaling on and around immune cells remains nebulous. In the central nervous system, biogenic amine transporters are regarded as the master regulators of neurotransmitter signaling. While we and others have shown macrophages express these transporters, relatively little is known of their function on these cells. To address these knowledge gaps, we interrogated the function of norepinephrine (NET) and dopamine (DAT) transporters on human monocyte-derived macrophages. We found that both NET and DAT are present and can uptake substrate from the extracellular space at baseline. Not only was DAT expressed in cultured macrophages, but it was also detected in a subset of intestinal macrophages in situ. Surprisingly, we discovered a NET-independent, DAT-mediated immuno-modulatory mechanism in response to lipopolysaccharide (LPS). LPS induced reverse transport of dopamine through DAT, engaging autocrine/paracrine signaling loop that regulated the macrophage response. Removing this signaling loop enhanced the pro-inflammatory response to LPS. Finally, we found that this DAT-immune axis was disrupted in disease. Collectively, our data introduce a novel role for DAT in the regulation of innate immunity during health and disease.

Neurochemistry of L-Glutamate Transport in the CNS: A Review of Thirty Years of Progress

2001 ◽  
Vol 66 (9) ◽  
pp. 1315-1340 ◽  
Author(s):  
Vladimir J. Balcar ◽  
Akiko Takamoto ◽  
Yukio Yoneda
Keyword(s):  
Molecular Biology ◽  
Glutamate Transport ◽  
Mammalian Brain ◽  
Activity Data ◽  
System A ◽  
Recent Developments ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Disease Analysis

The review highlights the landmark studies leading from the discovery and initial characterization of the Na+-dependent "high affinity" uptake in the mammalian brain to the cloning of individual transporters and the subsequent expansion of the field into the realm of molecular biology. When the data and hypotheses from 1970's are confronted with the recent developments in the field, we can conclude that the suggestions made nearly thirty years ago were essentially correct: the uptake, mediated by an active transport into neurons and glial cells, serves to control the extracellular concentrations of L-glutamate and prevents the neurotoxicity. The modern techniques of molecular biology may have provided additional data on the nature and location of the transporters but the classical neurochemical approach, using structural analogues of glutamate designed as specific inhibitors or substrates for glutamate transport, has been crucial for the investigations of particular roles that glutamate transport might play in health and disease. Analysis of recent structure/activity data presented in this review has yielded a novel insight into the pharmacological characteristics of L-glutamate transport, suggesting existence of additional heterogeneity in the system, beyond that so far discovered by molecular genetics. More compounds that specifically interact with individual glutamate transporters are urgently needed for more detailed investigations of neurochemical characteristics of glutamatergic transport and its integration into the glutamatergic synapses in the central nervous system. A review with 162 references.

scholarly journals Molecular and functional characterization of somatostatin-type signalling in a deuterostome invertebrate

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200172
Author(s):  
Ya Zhang ◽  
Luis Alfonso Yañez Guerra ◽  
Michaela Egertová ◽  
Cleidiane G. Zampronio ◽  
Alexandra M. Jones ◽  
...  
Keyword(s):  
Functional Characterization ◽  
The Body ◽  
Pharmacological Characterization ◽  
Cardiac Stomach ◽  
Physiological Processes ◽  
Pharmacological Tests ◽  
The Central Nervous System

Somatostatin (SS) and allatostatin-C (ASTC) are structurally and evolutionarily related neuropeptides that act as inhibitory regulators of physiological processes in mammals and insects, respectively. Here, we report the first molecular and functional characterization of SS/ASTC-type signalling in a deuterostome invertebrate—the starfish Asterias rubens (phylum Echinodermata). Two SS/ASTC-type precursors were identified in A. rubens (ArSSP1 and ArSSP2) and the structures of neuropeptides derived from these proteins (ArSS1 and ArSS2) were analysed using mass spectrometry. Pharmacological characterization of three cloned A. rubens SS/ASTC-type receptors (ArSSR1–3) revealed that ArSS2, but not ArSS1, acts as a ligand for all three receptors. Analysis of ArSS2 expression in A. rubens using mRNA in situ hybridization and immunohistochemistry revealed stained cells/fibres in the central nervous system, the digestive system (e.g. cardiac stomach) and the body wall and its appendages (e.g. tube feet). Furthermore, in vitro pharmacological tests revealed that ArSS2 causes dose-dependent relaxation of tube foot and cardiac stomach preparations, while injection of ArSS2 in vivo causes partial eversion of the cardiac stomach. Our findings provide new insights into the molecular evolution of SS/ASTC-type signalling in the animal kingdom and reveal an ancient role of SS-type neuropeptides as inhibitory regulators of muscle contractility.

scholarly journals Amino acids, taste circuits, and feeding behavior in Drosophila: towards understanding the psychology of feeding in flies and man

2007 ◽  
Vol 192 (3) ◽  
pp. 467-472 ◽  
Author(s):  
Christoph Melcher ◽  
Ruediger Bader ◽  
Michael J Pankratz
Keyword(s):  
Feeding Behavior ◽  
Functional Characterization ◽  
Relevant Information ◽  
Sensory Stimuli ◽  
Major Health ◽  
Obesity And Diabetes ◽  
The Central Nervous System ◽  
Complex Regulatory Network

Feeding can be regulated by a variety of external sensory stimuli such as olfaction and gustation, as well as by systemic internal signals of feeding status and metabolic needs. Faced with a major health epidemic in eating-related conditions, such as obesity and diabetes, there is an ever increasing need to dissect and understand the complex regulatory network underlying the multiple aspects of feeding behavior. In this minireview, we highlight the use of Drosophila in studying the neural circuits that control the feeding behavior in response to external and internal signals. In particular, we outline the work on the neuroanatomical and functional characterization of the newly identified hugin neuronal circuit. We focus on the pivotal role of the central nervous system in integrating external and internal feeding-relevant information, thus enabling the organism to make one of the most basic decisions – to eat or not to eat.

Phenotypical and functional characterization of Fey receptor I (CD64)-negative monocytes, a minor human monocyte subpopulation with high accessory and antiviral activity

1993 ◽  
Vol 23 (12) ◽  
pp. 3126-3135 ◽  
Author(s):  
Evelin Grage-Griebenow ◽  
Dirk Lorenzen ◽  
Rudolf Fetting ◽  
Hans-Dieter Flad ◽  
Martin Ernst
Keyword(s):  
Antiviral Activity ◽  
Functional Characterization ◽  
Human Monocyte ◽  
A Minor

scholarly journals Identification of Patulin from Penicillium coprobium as a Toxin for Enteric Neurons

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2776 ◽  
Author(s):  
Brand ◽  
Stoye ◽  
Guilherme ◽  
Nguyen ◽  
Baumgaertner ◽  
...  
Keyword(s):  
Nervous System ◽  
Neuronal Cell ◽  
Enteric Neurons ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Gut Microorganisms ◽  
Identification And Characterization ◽  
Effective Compound ◽  
Specific Impact

The identification and characterization of fungal commensals of the human gut (the mycobiota) is ongoing, and the effects of their various secondary metabolites on the health and disease of the host is a matter of current research. While the neurons of the central nervous system might be affected indirectly by compounds from gut microorganisms, the largest peripheral neuronal network (the enteric nervous system) is located within the gut and is exposed directly to such metabolites. We analyzed 320 fungal extracts and their effect on the viability of a human neuronal cell line (SH-SY5Y), as well as their effects on the viability and functionality of the most effective compound on primary enteric neurons of murine origin. An extract from P. coprobium was identified to decrease viability with an EC50 of 0.23 ng/µL in SH-SY5Y cells and an EC50 of 1 ng/µL in enteric neurons. Further spectral analysis revealed that the effective compound was patulin, and that this polyketide lactone is not only capable of evoking ROS production in SH-SY5Y cells, but also diverse functional disabilities in primary enteric neurons such as altered calcium signaling. As patulin can be found as a common contaminant on fruit and vegetables and causes intestinal injury, deciphering its specific impact on enteric neurons might help in the elaboration of preventive strategies.

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