China
Africa
Explore chapters and articles related to this topic
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).
Pharmacology of the lower urinary tract
Published in Jacques Corcos, David Ginsberg, Gilles Karsenty, Textbook of the Neurogenic Bladder, 2015
Several observations indicate that laminia propria ICs could be involved in the coordination of local bladder signaling processes. Mukerji et al.131 reported muscarinic (M2 and M3) receptors immunoreactivity on cells in the LP resembling IC, a finding confirmed by Grol et al.132 Mukerji et al.131 suggested that these cells could respond to cholinergic signaling. However, Sui et al.133 reported that suburothelial IC did not respond to carbachol but application of ATP elicited Ca2+ transients. P2Y6 receptors may mediate these excitatory responses.134 Further studies on spinal cord injured (SCI) rats, where laminia propria ICs are upregulated, suggested that this effect of ATP and other P2Y agonists could increase spontaneous contractile activity in the bladder.134 Xue et al.135 demonstrated that vimentin+ (and some KIT+) laminia propria ICs in the human bladder expressed hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, particularly HCN4. This channel is specialized for the If current, which is a characteristic of pacemaker cells, and it was suggested that HCN4 could be involved in the generation of spontaneous bladder activity during filling. However, further functional studies are needed to put these data into proper perspective.
Physiological Properties of the Lower Urinary Tract
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
A network of interstitial myofibroblast-like cells (ICs) has been identified in the suburothelium; these cells have demonstrable cell markers including vimentin (an intracellular filament protein seen in cells of mesodermal origin) and c-kit (a cell surface marker). They are connected by gap junctions containing connexin, Cx43, and are closely apposed to unmyelinated nerve endings (154,155). ICs may mediate urothelium-derived ATP responses by generating propagating depolarizing Ca2+ waves across the IC network, through P2Y6 activation, thus amplifying local responses to exogenous ATP (144,155). The ability of myofibroblasts to form functional networks can involve mechanisms other than via gap junctions: if two isolated cells are pushed together, each cell demonstrates enhanced responses to ATP without the obvious formation of gap junctions. The cellular adhesion molecule, Cadherin-11, has been demonstrated on myofibroblast membranes (156) and the activation of the membranes by intercellular adhesion may offer a mechanism. This enhancement of response is abolished by the c-kit receptor ligand glivec.
The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity
Published in Immunopharmacology and Immunotoxicology, 2018
Purinergic G protein-coupled receptor 6 (P2Y6), the high-affinity receptors for extracellular uridine diphosphate (UDP), is a member of GPCR40. P2Y6 is expressed on a variety of immune cells including T cells. The expression of P2Y6 has been found highly increased in activated T cells. Somers et al. showed that stimulation of activated T cells with the P2Y6 ligand UDP leads to TCR-dependent elevation of free calcium concentration41. Thus, P2Y6 might be associated with T cell activation. In fact, another research demonstrated that block of P2Y6 by MRS2578 significantly inhibits CD25 expression, IL-2 production and cytosolic Ca2 + level in T cells42.
Pathophysiological effect of bladder outlet obstruction on the urothelium
Published in Ultrastructural Pathology, 2018
Grzegorz Niemczyk, Katarzyna Czarzasta, Piotr Radziszewski, Paweł Włodarski, Agnieszka Cudnoch-Jędrzejewska
Induction of BOO in Sprague–Dawley rats leads to overexpression of P2X3 (P2X receptor family) in the urothelium.21 Likewise, Jiang et al. (2016), studying mucosa samples from patients with urodynamically diagnosed BOO, noted higher expression of the P2X3 receptors in comparison to control group.10 However, Silva et al. (2015) reported that P2X3 receptors almost disappeared in the urothelium along with P2X2 without amending P2Y6 expression in patients with BPH compared to controls. They suggest that this phenomenon could be explained by desensitization.20 Such discrepancy may be result of difference in both specimen and technique used.
Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts
Published in OncoImmunology, 2018
Gautier Stoll, Jonathan Pol, Vassili Soumelis, Laurence Zitvogel, Guido Kroemer
Figure 4 reveals 13 chemotactic receptors and chemokines that positively correlated with all identified cell subsets (irrespective of their stromal and leukocytic nature) contained in the tumor environment, regardless of the cancer type. This applies to CCR1,2,5; CXCR4; FPR1; ADORA2A; P2RY6,13,14; CCL18,19,21; and CXCL12. In other words, these factors appear intrinsically linked to the neoplastic process. Accordingly, CXCL12 and its receptor CXCR4 have been involved in promoting cancer proliferation, survival, invasion, metastasis, stemness and angiogenesis.52–57 CCR1 and its ligand CCL5 have been associated with cancer cell invasion and metastasis.58–60 Similar observations have been reported for the CCR2-CCL2, CCR5-CCL2,3,4,5, CCR7-CCL19,21 and CCR8-CCL18 axes.61–69 The role of FPR1 in tumor progression remains controversial as it has been associated with tumor invasion in colorectal cancer but with tumor suppression in gastric cancer.70,71 As far as P2RY6 is concerned, Placet et al. recently suggested its role in cancer cell survival.72 Overall, these 13 chemotactic receptors and chemokines may constitute universal targets for cancer therapy. Further consolidating the relevance of our results, additional correlations between tumor-infiltrating immune cell subtypes and chemokine/receptors across cancer types previously described in separate preclinical/clinical studies were found (Figure 4). Among these, we can mention the association between the infiltration of T cells and the requirement of the receptor ADORA273 or the role of CXCR3 and its ligands CXCL9 to 11 in the recruitment of CD8+ T cells, Th1 cells and NK cells.18 However, Figure 4 also revealed original interactions between immune cell subtypes. For instance, neutrophil infiltrates appeared negatively correlated with the chemokines CXCL9-11. Based on these results, the recruitment of T lymphocytes and neutrophils into the tumor microenvironment could be mutually exclusive. Indeed, a recent work demonstrating an inhibitory activity of CXCL9 peptides on neutrophil migration in murine models supporting such a hypothesis.74