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Bone Regeneration Effect of Cassia occidentalis Linn. Extract and Its Isolated Compounds
Published in Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay, Phytochemistry of Plants of Genus Cassia, 2021
Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay
Purinergic signalling modulates inflammatory and immune responses via extracellular adenine, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine. During inflammation, these extracellular biomolecules of purinergic signaling are regulated in immune cells by membrane-bound enzymes including ectonucleoside triphosphate diphosphohydrolase (E‐NTPDase) that breaks down ATP and ADP to AMP (Yegutkin, 2008) and ectoadenosine deaminase (E‐ADA) that is responsible for the removal of extracellular by deamination of adenosine and 2′‐deoxyinosine (Latini and Pedata, 2001). The activity of E‐NTPDase was increased and E‐ADA was decreased in the lymphocytes of complete Freund’s adjuvant (CFA)-induced arthritis, and oral quercetin treatment to arthritic rats reversed these changes along with the mitigation of arthritic scores. Serum adenosine level was higher in the arthritis rats compared to disease-free rats and quercetin significantly decreased this level. This report showed that the immunomodulatory effect of quercetin in arthritis involves the modulation of purinergic signaling (Saccol et al., 2019).
The mitotic phase of spermatogenesis
Published in C. Yan Cheng, Spermatogenesis, 2018
Recently, emerging players in the autocrine/paracrine regulation of spermatogonia have been identified. Sahin et al. have established a spermatogenesis regeneration model by first depleting spermatogenic cells except Aundiff using irradiation followed by the induction of spermatogonial differentiation by administration of gonadotrophin-releasing hormone agonist. Using this model, they observed that the Desert Hedgehog ligand Dhh, the Hedgehog receptor Ptc 2, and the receptor downstream signaling molecules Gli1 and Gli2 are expressed in Aundiff, suggesting the involvement of Hedgehog signaling in the autocrine regulation of spermatogonia.67 Apart from the involvement of cytokines and growth factors, a recent study has suggested the involvement of purinergic signaling in the autocrine/paracrine regulation of spermatogonia.68 Purinergic signaling is mediated by the binding of extracellular nucleotide or nucleoside such as ATP to the P2 receptor. Two subclasses of P2 receptors are metabotropic P2Y receptors (P2YRs) and ionotropic P2X receptors (P2XRs) that activate G-protein–coupled signaling and nucleotide-gated ion channels, respectively.69 By employing electrophysiological techniques, Flect et al. have shown that spermatogonia are sensitive to a board concentration range of extracellular ATP. They have further demonstrated two modes of ATP response: high-affinity (10-µM extracellular ATP) and low affinity (>300-µM extracellular ATP), which are mediated by P2X4 and P2X7 receptors, respectively.69 Further study is required to demonstrate the physiological role of purinergic signaling in the autocrine/paracrine regulation in spermatogonia.
Pulmonary – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
Purinergic signalling, a form of extracellular signalling mediated by purine nucleotides and nucleosides such as adenosine and ATP, plays a role in cough reflex hypersensitivity. Purinergic P2X receptors are a family of ligand-gated, non-selective cation channels that open in response to extracellular ATP and comprises seven members termed P2X1–P2X7. P2X3 receptors are now recognised as major players in mediating primary sensory effects of ATP and are found in airway nociceptive fibres. A novel P2X3 receptor antagonist (Gefapixant) has shown promising results in significantly reducing cough frequency in patients with unexplained chronic cough (UCC), suggesting that this might be an important treatable trait in patients with airway disease. In addition, treatments that modify the influence of higher centre control on the cough reflex, such as gabapentin, can also be useful. A systematic review of non-pharmacological interventions for patients with refractory chronic cough (RCC) also suggests benefit of the use of two to four sessions of a combination of education, cough suppression techniques, breathing exercises and counselling to achieve improvements in cough reflex sensitivity and cough-related quality of life for these individuals although further research is needed to more comprehensively establish effective components, treatment duration and frequency of this package. A smaller group of patients suffers of UCC, where no other disease exists than cough. Altered cough reflex sensitivity could also manifest as a reduced sensitivity or effectiveness of the cough reflex such as in relation to an underlying neuromuscular disease or medication. Such patients would then benefit from cough augmentation techniques.
Role of abnormal energy metabolism in the progression of chronic kidney disease and drug intervention
Published in Renal Failure, 2022
Xuyan Liu, Huasheng Du, Yan Sun, Leping Shao
Release of ATP from the cell allows it to initiate various extracellular purinergic signaling pathways. Extracellular ATP and ADP interact with the purinergic P2 receptors to promote inflammation. P2 receptors are subdivided into to two subclasses: the G protein-coupled P2Y receptors and the ATP-gated P2X nonselective ion channels. ATP primarily activates NLRP3 inflammasome through binding P2X7 receptors (P2X7R), resulting in secretion of IL-1β. In addition, ADP may stimulate IL-1 β production through the P2Y receptor expressed on macrophages [33]. In individuals with DKD, P2X7R and NLPR3 were upregulated compared with controls [26], and the increased expression of NLRP3 and IL-18 release were attenuated by P2X7R silencing in murine podocytes in another study [34]. The role of P2 receptors in renal fibrosis has been investigated in the unilateral ureteral obstruction model, which showed that TGF-β expression, macrophage infiltration and renal tubular fibrosis were reduced in P2X7R knockout mice compared with wild-type mice.
Shaddock (Citrus maxima) peels extract restores cognitive function, cholinergic and purinergic enzyme systems in scopolamine-induced amnesic rats
Published in Drug and Chemical Toxicology, 2022
Ayokunle O. Ademosun, Adeniyi A. Adebayo, Temitope V. Popoola, Ganiyu Oboh
Purinergic signaling influences the proper functioning of the nervous system, it is important in the perfection of functional activity between neurons, glial cells, and vascular cells in the CNS (Maria et al.2009). The decrease in these extracellular signaling molecules by an increase in ATPdase and ADA results in cognitive dysfunction. ATPdase activity in scopolamine-induced cognitive dysfunction rats is observed to be higher compared to the control and other groups. ATPdase catalyzes the breakdown of ATP into ADP, scopolamine increases the activity of this enzyme in the hippocampus of rat’s brain thereby decreasing the level of ATP this can result in loss of information in the brain: ATP is converted to cAMP by adenosine cyclase. cAMP is a second messenger that directly or indirectly affects information circulation within a system. An increase in ATPdase leads to a reduced level of cAMP and loss of information, eventually leading to cognitive dysfunction. Adenosine in the brain plays an important neuromodulatory role in the CNS in mammals.
Purinergic Signaling Involvement in Thymosin β4-mediated Corneal Epithelial Cell Migration
Published in Current Eye Research, 2020
Heung-Mo Yang, Shin Wook Kang, Jihye Sung, Kyeongsoon Kim, Hynda Kleinman
Purinergic signaling was first identified in 197211 and involves the P1 (adenosine) and P2 (nucleotide) receptor families.12 P2 receptors include P2X ion channel receptor subtypes and P2Y G protein-coupled receptors. The P2X7 receptor has an important role in many pathologies, including neural disorders, pain, tumor formation and growth, and inflammation.1–5 Moreover, the P2X7 receptor regulates both the proliferation and death of several cell types16,17, likely in part due to its activities as an ion channel and a cytolytic pore.18 P2X7 also interacts with actin, and this interaction has been related to a role in cell mobility.19–22 Therefore, using inhibitors that antagonize P2X7 may be a therapeutic strategy to treat various diseases.13 Recently, it was reported that the actin-binding protein, Tβ4, bound to ATP synthase and was involved in purinergic signaling.23 Although this study was performed only with vascular endothelial cells, it is likely that Tβ4 may mediate the corneal wound response via purinergic signaling. It was also reported that P2X7 allowed influx of extracellular calcium in response to activation by ATP.24