Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors

2019 ◽  
Vol 25 (26) ◽  
pp. 2892-2905 ◽  
Author(s):  
Sumit Jamwal ◽  
Ashish Mittal ◽  
Puneet Kumar ◽  
Dana M. Alhayani ◽  
Amal Al-Aboudi
Keyword(s):  
Nervous System ◽  
Therapeutic Potential ◽  
The Body ◽  
Membrane Receptors ◽  
Physiological Importance ◽  
Physiological Processes ◽  
Central Nervous Systems ◽  
Energy Consuming ◽  
Metabolic Dysfunctions ◽  
G Protein Coupled

Adenosine is a naturally occurring nucleoside and an essential component of the energy production and utilization systems of the body. Adenosine is formed by the degradation of adenosine-triphosphate (ATP) during energy-consuming processes. Adenosine regulates numerous physiological processes through activation of four subtypes of G-protein coupled membrane receptors viz. A1, A2A, A2B and A3. Its physiological importance depends on the affinity of these receptors and the extracellular concentrations reached. ATP acts as a neurotransmitter in both peripheral and central nervous systems. In the peripheral nervous system, ATP is involved in chemical transmission in sensory and autonomic ganglia, whereas in central nervous system, ATP, released from synaptic terminals, induces fast excitatory postsynaptic currents. ATP provides the energetics for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. Adenosine has been traditionally considered an inhibitor of neuronal activity and a regulator of cerebral blood flow. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosinerelated drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases. This review will summarize the therapeutic potential and recent SAR and pharmacology of adenosine and its receptor agonists and antagonists.

scholarly journals The Neural Regulation of Cancer

2020 ◽  
Vol 4 (1) ◽  
pp. 371-390
Author(s):  
Shawn Gillespie ◽  
Michelle Monje
Keyword(s):  
Nervous System ◽  
Crucial Role ◽  
The Body ◽  
Tissue Homeostasis ◽  
Neural Regulation ◽  
Physiological Processes

The nervous system is intimately involved in physiological processes from development and growth to tissue homeostasis and repair throughout the body. It logically follows that the nervous system has the potential to play analogous roles in the context of cancer. Progress toward understanding the crucial role of the nervous system in cancer has accelerated in recent years, but much remains to be learned. Here, we highlight rapidly evolving concepts in this burgeoning research space and consider next steps toward understanding and therapeutically targeting the neural regulation of cancer.

scholarly journals Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells

2016 ◽  
Vol 371 (1685) ◽  
pp. 20150040 ◽  
Author(s):  
Y. Wenger ◽  
W. Buzgariu ◽  
B. Galliot
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
G Protein Coupled Receptors ◽  
The Body ◽  
Neurogenic Genes ◽  
Cell Type Specific ◽  
The Impact ◽  
G Protein Coupled ◽  
Body Column ◽  
Compensatory Regulation

Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory–motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra , we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors ( Dlx , Dlx1 , DMBX1/Manacle , Ets1 , Gli3 , KLF11 , LMX1A , ZNF436 , Shox1 ), epitheliopeptides ( Arminins , PW peptide ), neurosignalling components ( CAMK1D , DDCl2 , Inx1 ), ligand-ion channel receptors ( CHRNA1 , NaC7 ), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.

scholarly journals On the influence of external environmental factors on the excretion of water by the kidneys

1929 ◽  
Vol 25 (10) ◽  
pp. 1020-1029
Author(s):  
G. S. Belenky
Keyword(s):  
Nervous System ◽  
External Environment ◽  
Clinical Diagnostics ◽  
The Body ◽  
Practical Reasons ◽  
Daily Work ◽  
Excretory Function ◽  
Physiological Processes ◽  
Conditions Of Work ◽  
Work And Life

More and more facts of the influence of the environment on the physiological processes of the body are accumulating at our disposal. The interaction between the environment and the activity of the entire nervous system (including the vegetative one), the activity of the cardiovascular system, digestive function, external and internal secretion, basic metabolism, etc. can be considered to a certain extent elucidated. We are interested in the question of the influence of the external environment on the activity of a healthy kidney, because this influence has to be taken into account already for practical reasons: 1) for preventive purposes, in order to be able to commensurate the strength and ability of the kidney to carry out its most important excretory function for the body with the load that in her daily work she receives from the external environment, from the conditions of work and life of her bearer, 2) for the purpose of clinical diagnostics when using, for example, a water sample, and also 3) in order to achieve the greatest effect of balneological drinking therapy.

scholarly journals Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 918 ◽  
Author(s):  
Kinga Tóth ◽  
Dorottya Ádám ◽  
Tamás Bíró ◽  
Attila Oláh
Keyword(s):  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
The Body ◽  
Future Research ◽  
Research Directions ◽  
Physiological Processes ◽  
Barrier Formation ◽  
The Central Nervous System ◽  
Future Research Directions ◽  
Pigmentation Disorders

The endocannabinoid system (ECS) has lately been proven to be an important, multifaceted homeostatic regulator, which influences a wide-variety of physiological processes all over the body. Its members, the endocannabinoids (eCBs; e.g., anandamide), the eCB-responsive receptors (e.g., CB1, CB2), as well as the complex enzyme and transporter apparatus involved in the metabolism of the ligands were shown to be expressed in several tissues, including the skin. Although the best studied functions over the ECS are related to the central nervous system and to immune processes, experimental efforts over the last two decades have unambiguously confirmed that cutaneous cannabinoid (“c[ut]annabinoid”) signaling is deeply involved in the maintenance of skin homeostasis, barrier formation and regeneration, and its dysregulation was implicated to contribute to several highly prevalent diseases and disorders, e.g., atopic dermatitis, psoriasis, scleroderma, acne, hair growth and pigmentation disorders, keratin diseases, various tumors, and itch. The current review aims to give an overview of the available skin-relevant endo- and phytocannabinoid literature with a special emphasis on the putative translational potential, and to highlight promising future research directions as well as existing challenges.

scholarly journals The evolution and mechanism of GPCR proton sensing

2020 ◽  
pp. jbc.RA120.016352
Author(s):  
Jacob B. Rowe ◽  
Nicholas J. Kapolka ◽  
Geoffrey J. Taghon ◽  
William M. Morgan ◽  
Daniel G. Isom
Keyword(s):  
Therapeutic Potential ◽  
G Protein Coupled Receptors ◽  
Hek293 Cells ◽  
Ph Sensing ◽  
Physiological Importance ◽  
Class A ◽  
Acidic Residues ◽  
Ph Range ◽  
G Protein Coupled ◽  
Direct Regulation

Of the 800 G protein-coupled receptors (GPCRs) in humans, only three (GPR4, GPR65, and GPR68) regulate signaling in acidified microenvironments by sensing protons (H+). How these receptors have uniquely obtained this ability is unknown. Here we show these receptors evolved the capability to sense H+ signals by acquiring buried acidic residues. Using our informatics platform pHinder, we identified a triad of buried acidic residues shared by all three receptors, a feature distinct from all other human GPCRs. Phylogenetic analysis shows the triad emerged in GPR65, the immediate ancestor of GPR4 and GPR68. To understand the evolutionary and mechanistic importance of these triad residues, we developed Deep Variant Profiling (DVP), a yeast-based technology that utilizes high-throughput CRISPR to build and profile large libraries of GPCR variants. Using DVP and GPCR assays in HEK293 cells, we assessed the pH-sensing contributions of each triad residue in all three receptors. As predicted by our calculations, most triad mutations had profound effects consistent with direct regulation of receptor pH sensing. Additionally, we found that an allosteric modulator of many class A GPCRs, Na+, synergistically regulated pH sensing by maintaining the pKa values of triad residues within the physiologically relevant pH range. As such, we show that all three receptors function as coincidence detectors of H+ and Na+. Taken together, these findings elucidate the molecular evolution and long-sought mechanism of GPR4, GPR65, and GPR68 pH sensing, and provide pH-insensitive variants that should be valuable for assessing the therapeutic potential and (patho)physiological importance of GPCR pH sensing.

scholarly journals A REVIEW ARTICLE ON THE PHYSIOLOGICAL IMPORTANCE OF SAMANA VAYU IN RELATION TO THE ENTERIC NERVOUS SYSTEM

2021 ◽  
Vol 9 (12) ◽  
pp. 3108-3112
Author(s):  
Neha Sajwan ◽  
Rajesh Kumar Sharma ◽  
Dinesh Chandra Sharma
Keyword(s):  
Nervous System ◽  
Gastrointestinal Tract ◽  
Enteric Nervous System ◽  
Physiological Activity ◽  
Review Article ◽  
The Body ◽  
Waste Products ◽  
Physiological Importance ◽  
Sacral Segment ◽  
All Diseases

Ayurveda is a science that has been around for thousands of years and has proven to be beneficial to humans. Ayurveda is based on the tridosha theory. Vata, one of three doshas, plays an essential and major part in both healthy and unhealthy conditions, according to acharya sushruta dosha, dhatu and mala maintain our body. There are five types of vata- prana, udan, samana, vyan and apaan vayu. Among these five doshas samana vayu is situated near jatharagni and circulate all over the GIT tract. It helps in the division of essence and waste products, as well as the movement of the gastrointestinal tract, by stimulating the agni. In the body, jatharagni takes the form of pachak pitta, one of the pitta subtypes. Agnimandhya is responsible for all diseases, as we all know. The fire is fueled by samana vayu, who keeps it balanced. As a result, samana vayu might be regarded to play a specialized role in digestion. All of the samana vayu's functions can be compared to the physiological functions of the enteric nervous system and the sympathetic and parasympathetic supply of the Autonomic nervous system to the gastrointestinal tract. In this article, an attempt is made to correlate the physiological activity of samana vayu with the enteric nervous system. Keywords: Samana vayu, Prana vayu, Apan vayu, Sacral Segment.

scholarly journals An Autonomous Cannabinoid System in Islets of Langerhans

2021 ◽  
Vol 12 ◽  
Author(s):  
Kanikkai Raja Aseer ◽  
Josephine M. Egan
Keyword(s):  
Insulin Secretion ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Cell Types ◽  
Β Cells ◽  
Β Cell ◽  
Glucose And Lipid Metabolism ◽  
Physiological Processes ◽  
Islet Physiology ◽  
G Protein Coupled

While endocannabinoids (ECs) and cannabis were primarily studied for their nervous system effects, it is now clear that ECs are also produced in the periphery where they regulate several physiological processes, including energy storage, glucose and lipid metabolism, insulin secretion and synthesis, and hepatocyte function. Within islet of Langerhans there is an autonomous EC system (ECS). Beta (β)-cells contain all the enzymes necessary for EC synthesis and degradation; ECs are generated in response to cellular depolarization; their paracrine influence on β-cells is mostly through the cannabinoid 1 receptor (CB1R) that is present on all β-cells; they modulate basal and glucose- and incretin-induced insulin secretion, and β-cell responses to various stressors. Furthermore, there is now accumulating evidence from preclinical studies that the autonomous islet ECS is a key player in obesity-induced inflammation in islets, and β-cell damage and apoptosis from many causes can be mitigated by CB1R blockers. We will thoroughly review the literature relevant to the effects of ECs and their receptors on β-cells and the other cell types within islets. Therapeutic potential of agents targeting EC/CB1R and CB2R is highly relevant because the receptors belong to the druggable G protein-coupled receptor superfamily. Present research in the ECS must be considered preliminary, especially with regards to human islet physiology, and further research is needed in order to translate basic cellular findings into clinical practice and the use of safe, clinically approved CBR modulators with and without glucose lowering combinations presently in therapeutic use for diabetes and obesity needs to be studied.

Biosocial Resonation: A Conceptual Model of the Links between Social Behavior and Physical Illness

1974 ◽  
Vol 5 (4) ◽  
pp. 401-410 ◽  
Author(s):  
Gordon E. Moss
Keyword(s):  
Nervous System ◽  
Communication Networks ◽  
Social Communication ◽  
Direct Contact ◽  
The Body ◽  
Social Variables ◽  
Physiological Variables ◽  
Physiological Processes ◽  
Correct Information ◽  
The Individual

If sociomedical research is to move beyond the stage of repeatedly reporting correlations between social variables and disease, a viable conceptualization of the connection between social and physiological variables must be developed. We suggest that subjective interpretations of information perceived in a situation as congruous or incongruous with learned expectations is the key point of articulation. Each individual has an information repertoire derived from social interaction and direct contact with the non-social environment. If the individual's perceptions of the situation are not congruous with his information repertoire, he is likely to experience activation of the autonomic nervous system and related neuroendocrine and somatic processes. If these physiological processes are intense and/or prolonged enough, they may alter the body's resistance to infectious organisms, temporarily or irreversibly damage the body or reduce behavioral efficiency, increasing the likelihood of accidents. At the same time, encountering of information incongruities may lead to rejection by the individual of the source of the invalidated information. If this source is a social network, the member may become alienated from the network. If this alienation is shared by others, it may lead to social change. Social communication networks protect their members from incongruities by teaching them correct information, by isolating them from incongruous information, by explaining incongruities encountered so they are no longer perceived as incongruous, and by providing means of relieving tensions produced by encounters with incongruities.

scholarly journals Role of Cannabinoid Receptors in Psychological Disorder

2020 ◽  
Vol 3 (4) ◽  
pp. 199-208
Author(s):  
Ambika Nand Jha ◽  
Dhaval M Patel
Keyword(s):  
Cannabinoid Receptors ◽  
Biological Effects ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
The Body ◽  
Psychological Disorder ◽  
Physiological Processes ◽  
Neurochemical Changes ◽  
G Protein Coupled

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system. Cannabinoid CB1 and CB2 receptors are G protein-coupled receptors present from the early stages of gestation, which is involved in various physiological processes, including appetite, pain-sensation, mood, and memory. Due to the lipophilic nature of cannabinoids, it was initially thought that these compounds exert several biological effects by disrupting the cell membrane nonspecifically. Recent biochemical and behavioral findings have demonstrated that blockade of CB1 receptors engenders antidepressant-like neurochemical changes (increases in extracellular levels of monoamines in cortical but not subcortical brain regions) and behavioral effects consistent with antidepressant/antistress activity. We aim to define various roles of cannabinoid receptors in modulating signaling pathways and association with several pathophysiological conditions.

Nerve and muscle

2012 ◽  
Keyword(s):  
Skeletal Muscle ◽  
Nervous System ◽  
Smooth Muscle ◽  
Cardiac Muscle ◽  
Clinical Symptoms ◽  
Sensory Information ◽  
The Body ◽  
Membrane Receptors ◽  
Excitable Cells ◽  
Chemical Synapses

Higher animals have four basic tissue types: epithelial tissue, connective tissue, nervous tissue, and muscle. Of these, nerve and muscle are grouped together as ‘excitable cells’ because the cell membrane has the ability to vary membrane ion conductance and membrane voltage so as to transmit meaningful signals within and between cells. Within excitable cells information is transmitted using either an amplitude-modulated (AM) code using slow, electrotonic potentials, or a frequency-modulated (FM) code when signalling is by action potentials. Much of the signalling between excitable cells occurs at chemical synapses where a chemical neurotransmitter is released from presynaptic cells and then interacts with postsynaptic membrane receptors. Clinical symptoms can arise when the release of chemical neurotransmitters is disturbed, or when availability of postsynaptic receptors is altered. Thus, a reduction in dopamine release from basal ganglia substantia nigra cells is found in Parkinson’s disease, while myasthenia gravis results from loss of nicotinic acetylcholine receptors at the neuromuscular junction of skeletal muscle. Sometimes transmission from cell to cell is not by chemical neurotransmitter but by electrical synapses, where gap-junctions provide direct electrical connectivity. Transmission between cardiac muscle cells occurs in this way. Some cardiac arrhythmias, such as Wolff –Parkinson–White syndrome, are a consequence of an abnormal path of electrical conduction between cardiac muscle fibres. Sensory cells on and within the body pass information via afferent pathways from the peripheral nervous system into the central nervous system (CNS). CNS processes and sensory information are integrated to produce outputs from the CNS. These outputs pass by various efferent routes to the effector organs: skeletal muscle, cardiac muscle, smooth muscle, and glands. It is through these effectors that the CNS is able to exert control over the body and to interact with the environment. Alterations of function anywhere in the afferent, integrative, or efferent aspects of the system, as well as defects in the effectors themselves, are likely to lead to significant clinical symptoms and signs. The efferent outflow from the CNS has two major components. One, the somatic nervous system, innervates only skeletal muscle. The other is the autonomic nervous system (ANS), which innervates cardiac muscle, smooth muscle, and the glands of the viscera and skin.

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