Non-neuronal regulation and repertoire of cholinergic receptors in organs

2010 ◽  
Vol 1 (5-6) ◽  
pp. 357-366
Author(s):  
Tsuyoshi Sato ◽  
Dai Chida ◽  
Takanori Iwata ◽  
Michihiko Usui ◽  
Kouki Hatori ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Cholinergic Receptors ◽  
Target Cells ◽  
Neuronal Mechanism ◽  
Neuronal Regulation ◽  
Cholinergic Pathway

AbstractMany studies on the cholinergic pathway have indicated that cholinergic receptors, which are widely expressed in various cells, play an important role in all body organs. In this review, we present the concept that cholinergic responses are regulated through a neuronal or non-neuronal mechanism. The neuronal mechanism is a system in which acetylcholine binds to cholinergic receptors on target cells through the nerves. In the non-neuronal mechanism, acetylcholine, produced by neighboring cells in an autocrine/paracrine manner, binds to cholinergic receptors on target cells. Both mechanisms subsequently lead to physiological and pathophysiological responses. We also investigated the subunits/subtypes of cholinergic receptors on target cells, physiological and pathophysiological responses of the organs via cholinergic receptors, and extracellular factors that alter the subtypes/subunits of cholinergic receptors. Collectively, this concept will elucidate how cholinergic responses occur and will help us conduct further experiments to develop new therapeutic agents.

scholarly journals Delivery of Therapeutic Agents to the Central Nervous System and the Promise of Extracellular Vesicles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 492
Author(s):  
Charlotte A. René ◽  
Robin J. Parks
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Significant Barrier ◽  
The Central Nervous System ◽  
Delivery Vehicles

The central nervous system (CNS) is surrounded by the blood–brain barrier (BBB), a semipermeable border of endothelial cells that prevents pathogens, solutes and most molecules from non-selectively crossing into the CNS. Thus, the BBB acts to protect the CNS from potentially deleterious insults. Unfortunately, the BBB also frequently presents a significant barrier to therapies, impeding passage of drugs and biologicals to target cells within the CNS. This review provides an overview of different approaches to deliver therapeutics across the BBB, with an emphasis in extracellular vesicles as delivery vehicles to the CNS.

scholarly journals Extracellular Vesicles as Biological Shuttles for Targeted Therapies

2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Special Focus ◽  
Pathological Conditions ◽  
Critical Issues ◽  
Membrane Bound ◽  
And Function ◽  
Potential Use

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.

On Cancer Nanotechnology

2010 ◽  
Vol 441 ◽  
pp. 307-332
Author(s):  
Rita Bosetti ◽  
Lode Vereeck
Keyword(s):  
Quality Of Life ◽  
Cancer Research ◽  
Side Effects ◽  
Cancer Biology ◽  
Causes Of Death ◽  
Poor Quality ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Patients Experience

Although governments invest billions of dollars in cancer research, cancer remains one of the major causes of death worldwide (Liu et al., 2007). During the last decades, outstanding results have been attained in fundamental cancer biology but, unfortunately, they have not been translated in even distantly comparable progressions in the clinic. The main reason for this gap being the inability to administer therapeutic agents so that they can reach target cells without or with minimal side-effects (Ferrari, 2005). Today, scientists are faced with the recognition that very few molecules reach the desired locations and thus fail to selectively reach the target cells. Consequently, patients experience a very poor quality of life (Ferrari, 2004; Ferrari, 2005; Chan, 2006).

scholarly journals Extracellular Vesicles: Versatile Nanomediators, Potential Biomarkers and Therapeutic Agents in Atherosclerosis and COVID-19-Related Thrombosis

2021 ◽  
Vol 22 (11) ◽  
pp. 5967
Author(s):  
Adriana Georgescu ◽  
Maya Simionescu
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Special Section ◽  
Surface Characteristics ◽  
Therapeutic Agents ◽  
High Rate ◽  
Target Cells ◽  
Cytoplasmic Proteins ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Transfer Of Information

Cells convey information among one another. One instrument employed to transmit data and constituents to specific (target) cells is extracellular vesicles (EVs). They originate from a variety of cells (endothelial, immune cells, platelets, mesenchymal stromal cells, etc.), and consequently, their surface characteristics and cargo vary according to the paternal cell. The cargo could be DNA, mRNA, microRNA, receptors, metabolites, cytoplasmic proteins, or pathological molecules, as a function of which EVs exert different effects upon endocytosis in recipient cells. Recently, EVs have become important participants in a variety of pathologies, including atherogenesis and coronavirus disease 2019 (COVID-19)-associated thrombosis. Herein, we summarize recent advances and some of our own results on the role of EVs in atherosclerotic cardiovascular diseases, and discuss their potential to function as signaling mediators, biomarkers and therapeutic agents. Since COVID-19 patients have a high rate of thrombotic events, a special section of the review is dedicated to the mechanism of thrombosis and the possible therapeutic potential of EVs in COVID-19-related thrombosis. Yet, EV mechanisms and their role in the transfer of information between cells in normal and pathological conditions remain to be explored.

scholarly journals Identification of the targets of T cell receptor therapeutic agents and cells by use of a high throughput genetic platform

2018 ◽  
Author(s):  
Ron S. Gejman ◽  
Heather F. Jones ◽  
Martin G. Klatt ◽  
Aaron Y. Chang ◽  
Claire Y. Oh ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
High Throughput ◽  
Cancer Therapeutics ◽  
Cell Receptor ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Mhc I ◽  
Immunological Assays

T cell receptor (TCR)-based therapeutic cells and agents have emerged as a new class of effective cancer therapeutics. These therapies work on cells that express intracellular cancer-associated proteins by targeting peptides displayed on major histocompatibility complex receptors. However, cross-reactivities of these agents to off-target cells and tissues have resulted in serious, sometimes fatal, adverse events. We have developed a high throughput genetic platform (termed “PresentER”) that encodes MHC-I peptide minigenes for functional immunological assays as well as for determining the reactivities of TCR-like therapeutic agents against large libraries of MHC-I ligands. In this report, we demonstrate that PresentER can be used to identify the on-and-off targets of T cells and TCR mimic antibodies using in vitro co-culture assays or binding assays. We find dozens of MHC-I ligands that are cross-reactive with two TCR mimic antibodies and two native TCRs and that are not easily predictable by other methods.

scholarly journals The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 257-267 ◽  
Author(s):  
D Metcalf
Keyword(s):  
Functional Activity ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Bacterial Cells ◽  
Rapid Progress ◽  
Colony Stimulating Factors ◽  
Functional Activities ◽  
Macrophage Colony ◽  
Molecular Nature

Abstract Rapid progress has occurred recently in characterizing the molecular nature of the specific glycoprotein colony-stimulating factors (CSFs) controlling the proliferation; and some functional activities of granulocytes and monocyte-macrophages. All four known murine CSFs have been purified, and cDNAs for two have been cloned and expressed by mammalian and bacterial cells. Similarly, three human CSFs have been purified, and cDNAs for two cloned and expressed. This work has opened up the exciting prospects of testing the effects of these recombinant CSFs on hematopoiesis in vivo. Each CSF has a broader range of hematopoietic target cells than previously suspected, and it is now clear that the CSFs are not simply proliferative stimuli but can also regulate the functional activity of mature cells. There are increasing reasons to believe that these CSFs will be useful therapeutic agents in stimulating hematopoietic regeneration in leukopenic states and the functional activity of granulocytes and monocytes in infections.

scholarly journals The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 257-267 ◽  
Author(s):  
D Metcalf
Keyword(s):  
Functional Activity ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Bacterial Cells ◽  
Rapid Progress ◽  
Colony Stimulating Factors ◽  
Functional Activities ◽  
Macrophage Colony ◽  
Molecular Nature

Rapid progress has occurred recently in characterizing the molecular nature of the specific glycoprotein colony-stimulating factors (CSFs) controlling the proliferation; and some functional activities of granulocytes and monocyte-macrophages. All four known murine CSFs have been purified, and cDNAs for two have been cloned and expressed by mammalian and bacterial cells. Similarly, three human CSFs have been purified, and cDNAs for two cloned and expressed. This work has opened up the exciting prospects of testing the effects of these recombinant CSFs on hematopoiesis in vivo. Each CSF has a broader range of hematopoietic target cells than previously suspected, and it is now clear that the CSFs are not simply proliferative stimuli but can also regulate the functional activity of mature cells. There are increasing reasons to believe that these CSFs will be useful therapeutic agents in stimulating hematopoietic regeneration in leukopenic states and the functional activity of granulocytes and monocytes in infections.

scholarly journals ANTIAPOPTOSIS ACTIVITY OF PLANT POLYPRENYLPHOSPHATE AGAINST MACROPHAGE TARGET CELLS INFECTED WITH THE MURINE ENCEPHALOMYELITIS VIRUS

2019 ◽  
Vol 19 (1S) ◽  
pp. 207-209
Author(s):  
T N Kozhevnikova ◽  
A V Sanin ◽  
S V Ozherelkov
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Antioxidant Activity ◽  
Nervous System ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Plant Origin ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System ◽  
Multiple Sclerosis Treatment

Antiapoptosis activity of plant polyprenylphosphate against macrophage target cells infected with the murine encephalomyelitis virus. Infection caused by the Theiler’s murine encephalomyelitis virus (TMEV) is regarded as an experimental model of multiple sclerosis, since both of these diseases are characterized by similar pathology of the central nervous system tissues and involvement of the immune system in the development of the demielinization. The aim of the work was to study the effect of plant-derived polyprenylphosphate (PP) on the apoptosis of infected target cells. We showed that PP reduced apoptosis of macrophage target cells infected with TMEV. It is known that in the protocol of multiple sclerosis treatment some medicines possessing immunomodulatory, antiviral, anti-inflammatory and antioxidant activity are used. Since PPs of plant origin also have all these activities, the prospects of their use as therapeutic agents are discussed.

Is the input to a GABAergic or cholinergic synapse the sole asymmetry in rabbit's retinal directional selectivity?

1997 ◽  
Vol 14 (1) ◽  
pp. 39-54 ◽  
Author(s):  
Norberto M. Grzywacz ◽  
John S. Tootle ◽  
Franklin R. Amthor
Keyword(s):  
Ganglion Cells ◽  
Cholinergic Receptors ◽  
Cholinergic Antagonists ◽  
Directional Selectivity ◽  
Spike Generation ◽  
Cholinergic Synapse ◽  
Inhibition Model ◽  
Preferred Direction ◽  
Cholinergic Pathway ◽  
Alternate Model

AbstractWe examined contrast, direction of motion, and concentration dependencies of the effects of GABAergic and cholinergic antagonists, and anticholinesterases on responses to movement of On—Off directionally selective (DS) ganglion cells of the rabbit's retina. The drugs tested were curare and hexamethonium bromide (cholinergic antagonists), physostigmine (anticholinesterase), and picrotoxin (GABAergic antagonist). They all reduced the cells' directional selectivity, while maintaining their preferred-null axis. However, cholinergic antagonists did not block directional selectivity completely even at saturating concentrations. The failure to eliminate directional selectivity was probably not due to an incomplete blockade of cholinergic receptors. In a extension of a Masland and Ames (1976) experiment, saturating concentrations of antagonists blocked the effects of exogenous acetylcholine or nicotine applied during synaptic blockade. Consequently, a noncholinergic pathway may be sufficient to account for at least some directional selectivity. This putative pathway interacts with the cholinergic pathway before spike generation, since physostigmine eliminated directional selectivity at contrasts lower than those saturating responses. This elimination apparently resulted from cholinergic-induced saturation, since reduction of contrast restored directional selectivity. Under picrotoxin, directional selectivity was lost in 33% of the cells regardless of contrast. However, 47% maintained their preferred direction despite saturating concentrations of picrotoxin, and 20% reversed the preferred and null directions. Therefore, models based solely on a GABAergic implementation of Barlow and Levick's asymmetric-inhibition model or solely on a cholinergic implementation of asymmetric-excitation models are not complete models of directional selectivity in the rabbit. We propose an alternate model for this retinal property.

scholarly journals Lipid-Based Nanoparticles in Cancer Diagnosis and Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew D. Miller
Keyword(s):  
Cancer Diagnosis ◽  
Therapeutic Agents ◽  
Imaging Agents ◽  
Chemical Components ◽  
Target Cells ◽  
Functional Requirements ◽  
Cancer Disease ◽  
Diverse Range ◽  
Diagnosis And Therapy ◽  
Cancer Diagnosis And Therapy

Today, researchers are constantly developing new nanomaterials, nanodevices, and nanoparticles to meet unmet needs in the delivery of therapeutic agents and imaging agents for cancer therapy and diagnosis, respectively. Of particular interest here are lipid-based nanoparticles (LNPs) that are genuine particles (approximately 100 nm in dimension) assembled from varieties of lipid and other chemical components that act collectively to overcome biological barriers (biobarriers), in order for LNPs to preferentially accumulate in or around disease-target cells for the functional delivery of therapeutic agents for treatment or of imaging agents for diagnosis. The capabilities of these LNPs will clearly vary depending on functional requirements, but the nanoscale allows for an impressive level of diversity in capabilities to enable corresponding LNPs to address an equally diverse range of functional requirements. Accordingly, LNPs should be considered appropriate vehicles to provide an integrated, personalized approach to cancer diagnosis and therapy in future cancer disease management.

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