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Purinergic Regulation of Bile Ductular Secretion
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Like P1 receptors, P2Y receptors are G protein coupled. However, unlike P1 receptors, P2Y receptors are linked via phospholipase C to inositol trisphosphate-mediated increases in cytosolic calcium (Ca2+i) and diacyl glycerol-mediated activation of protein kinase C, rather than activation of cAMP (Fig. 1). At least six P2Y receptor subtypes, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, and P2Y12, have been cloned and characterized in mammals.8–15 The first four members of this family couple only to phospholipase C, while P2Y11 also increases cAMP, and P2Y12 suppresses cAMP.1 These receptors are all activated by distinct nucleotides. The pharmacological activation of these receptors is summarized in (Table 1).
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).
Medications for endovascular therapy
Published in Peter A. Schneider, Endovascular Skills: Guidewire and Catheter Skills for Endovascular Surgery, 2019
Most patients with peripheral vascular disease will be on some antiplatelet agent. Lifelong once-a-day aspirin therapy is common. Aspirin (acetylsalicylic acid) blocks the thromboxane A2 pathway to platelet aggregation. Dual antiplatelet therapy is also common, especially after a coronary stent or other implantable vascular device. The most commonly used antiplatelet agent after aspirin is clopidogrel, and this is commonly paired with aspirin when dual antiplatelet therapy is indicated. The usual daily oral dose of clopidogrel is 75 mg. The onset of action is approximately 1–2 hours and it lasts 5–10 days. When more immediate effect is required, a loading dose of 300 mg can be administered. Clopidogrel functions by inhibiting the P2Y receptor on platelets. Patients on dual antiplatelet agents can be treated with open surgery or hybrid open and endovascular procedures, but caution must be taken to avoid postoperative bleeding. In some procedures, such as carotid stenting or tibial interventions, dual antiplatelet agents are a requirement. Patients receiving a drug-coated balloon or drug-eluting stent in the noncoronary vasculature also require dual antiplatelet therapy, at least for a period of time after the procedure, typically 1–3 months.
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.
Systems biomarker characteristics of circulating alkaline phosphatase activities for 48 types of human diseases
Published in Current Medical Research and Opinion, 2022
Wenhao Su, Tong Qiu, Meng Zhang, Cui Hao, Pengjiao Zeng, Zhangfeng Huang, Wenxing Du, Tianxiang Yun, Yunpeng Xuan, Lijuan Zhang, Yachong Guo, Wenjie Jiao
ALP has been extensively studied since 1979. Multiple human diseases, including liver diseases, bone metastases in advanced cancer, gastrointestinal inflammation, vascular calcification, and stroke, have been associated with increased circulating ALP activities. There was evidence suggesting that ALP participated in various pathophysiological processes14,26–30. Purinergic signals play an essential role in the regulation of immune response. Extracellular ATP promotes inflammation through P2Y receptors, while adenosine has the opposite effect, which is transmitted by P1 receptors. ALP could catalyze the conversion of pro-inflammatory adenosine triphosphate into anti-inflammatory adenosine. Therefore, the increased ALP activities might be the response of cells to inflammatory stimuli, which might explain the increased ALP activity under sepsis and other inflammatory conditions28,41–44. In addition, purinergic signals may be involved, such as in atherosclerosis45 and chronic inflammation-related diseases. Studies have shown an association between reduced nucleotide signaling via the P2Y receptor and increased calcification of arterial intima and vascular smooth muscle cells in P2Y2R−/− mice46. The accelerated arterial calcification is seen in mice overexpressing TNALP in endothelial cells47 and VSMC48, suggesting that ALP might be part of the vascular defense mechanism during inflammation.
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