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Pharmacotherapy of Neurochemical Imbalances
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar, Suvarna Ingale
ATP has now also established its role as a transmitter through its widespread receptor-mediated actions in the body. ATP binds with two types of receptors, P2X and P2Y receptors. P2X receptors are ligand-gated ion channel receptors subdivided into seven subtypes (P2X1 to P2X7). P2X receptors are widely distributed all over the body. P2X1 and P2X2 receptors are found in the dorsal horn, and hence play an important role in sensory transmission. P2Y receptors are GPCRs and there are eight subtypes of P2Y receptors such as P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14 (Rang et al., 2011; Edward and Gibb, 1993; Barrett et al., 2009; Webster, 2001).
Preclinical Antidepressant-Like Effects of Terpenes, Polyphenolics, and Other Non-Flavonoid Phytochemicals
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
Chronic intraperitoneal administration of palmatine exerted antidepressant-like effects in mice that had been subjected to chronic unpredictable stress, as well as in non-stressed mice. In both groups, palmatine decreased duration of immobility in the forced swim and tail suspension tests. The highest doses of palmatine restored sucrose preference in stressed mice. Palmatine was further found to reverse stress-induced increases in brain catalase and MAO-A activities, brain lipid peroxidation, and plasma levels of nitrite and corticosterone.160 Palmatine also showed antidepressant-like effects in diabetic rats. Palmatine decreased immobility in the forced swim test and restored appetite for sucrose. Palmatine decreased levels of TNF-α and IL-1β in the hippocampus of the rats. Another effect was a decrease in the number of P2X7 receptors in the hippocampus. Increases in the density of those receptors in the hippocampus is associated with both pain and depression-like behaviors.161
Mitochondrial Dysfunction and Allergic Disease
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Kritika Khanna, Anurag Agrawal
Mitochondria generate high amounts of ATP that are released in the cytoplasm where they serve as the main source of energy for the cell. Under physiological conditions, the ATP secreted out of the cells is maintained in a proper concentration by the action of ecto ATP/ADPases (Lohman, Billaud, and Isakson 2012). However, under pathological conditions, the levels of extracellular ATP increase and serve as “alert signals” for the immune system. Extracellular ATP is recognized by purinergic receptor – P2X7, an ATP gated channel receptor, which is highly expressed on immune cells. Stimulation of these receptors activates the NLRP3 inflammasome signalling and induces inflammatory chemotaxis (Iyer et al. 2009).
Classification and management strategies for paediatric chronic nonbacterial osteomyelitis and chronic recurrent multifocal osteomyelitis
Published in Expert Review of Clinical Immunology, 2023
Shabnam Singhal, Caren Landes, Rajeev Shukla, Liza J McCann, Christian M Hedrich
The transmembrane P2×7 receptor is a key regulator of inflammasome activity (Figure 1). Activation of P2×7 with ATP results in potassium efflux from cells and NRLP3 inflammasome assembly. Increased P2×7 activation had previously been linked to increased inflammasome activity in the context of Majeed syndrome (Box 1, below), an early-onset systemic autoinflammatory disease with nonbacterial osteomyelitis as a key feature [53]. Notably, increased expression and activity of P2×7 has been reported in a SAPHO patient who exhibited increased inflammasome assembly and release of IL-1β when compared to controls after priming of monocytes with LPS or their stimulation with ATP [54,55]. The authors furthermore showed that, in monocytes from the SAPHO patient, blockade of P2×7 fully abolished IL-1β secretion and successfully treated the patient with the recombinant IL-1 receptor antagonist [56]. Recently, rare and common damaging variants of P2RX7 have been reported in a large national cohort of CNO/CRMO patients (n = 191, Germany) [57]. Functional assays in genetically modified THP-1 monocyte cell-lines linked CNO-associated variants with increased pro-inflammatory signaling but reduced cell death/pyroptosis when compared to wild-type P2×7. This links variants in P2×7 and associated effects on downstream inflammasome assembly and pyroptosis with the pathophysiology of CNO/CRMO that may result in future patient stratification and target-directed treatments (P2×7 modulation, IL-1 blocking strategies).
P2X3-P2X7 SNPs and gene-gene and gene-environment interactions on pediatric asthma
Published in Journal of Asthma, 2023
Lingxue Li, Bing Wei, Jingjing Jia, Mo Li, Mengyang Ren, Shinan Zhang
Purinergic receptors (P2X) are gated cation channels with adenosine triphosphate (ATP) as the ligand (4). After ATP binds to P2X, it activates downstream related signaling pathways, causing target cells to produce specific biological responses, in addition, the study confirmed that P2 receptor antagonists mitigate airway hyperreactivity triggered by activating dendritic cells in extracellular ATP, and accumulating data suggest that ATP levels are enhanced in secretions from airway injury and respiratory disease (5,6). ATP plays an important regulatory role in the release of histamine from mast cells and may be involved in allergic/asthmatic responses (7–9), of which P2X3 and P2X7 are two subtypes. P2X3 gene on the chromosome 11q12.1 is predominantly expressed on vagal C or A∂ fibers in the airway and is the core of cough induction and sensitization (10,11). P2X7 gene on the chromosome 12q24.31 is highly expressed in immune cells, activates the nuclear factor Kappa B (NF-κB)/cysteinyl aspartate-specific proteases-1 (Caspase-1) pathway to releases interleukin-1β (IL-1β), which is involved in the inflammatory response (12). Studies have confirmed that sensitization and exposure models of allergic asthma in P2X7 knockout mice show decreased airway reactivity (13). Therefore, we speculate that the alteration of P2X3 and P2X7 genes expression may be related to asthma.
Advances in understanding the mechanisms of retinal degenerations
Published in Clinical and Experimental Optometry, 2020
It is well known that ATP produced by mitochondria plays a critical role in energy metabolism. However, ATP can also act as a signalling molecule when it is located in the extracellular space.12 The cellular effects of ATP are mediated by two types of receptors: there are seven different types of P2X receptors that are all ion channels that pass cations when ATP binds13 (Figure 1). Figure 1 shows the structure of P2X7 – it consists of a short N‐terminal region, two transmembrane forming regions and a long intracellular C‐terminus. The large extracellular loop is important for ATP binding and opening the ion channel so that sodium and calcium ions can pass into the cell causing depolarisation. In contrast to P2X receptors, the eight P2Y receptors belong to the large family of seven transmembrane G protein coupled receptors.13