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Neuropeptides and Cell Proliferation
Published in Edwin E. Daniel, Neuropeptide Function in the Gastrointestinal Tract, 2019
Following the binding of mitogenic peptides to cell membrane receptors, a number of intracellular messenger systems transmit appropriate signals to the cellular genome. These are rapid events which trigger the cellular responses necessary to enter and traverse G1 of the cell cycle and include: (1) changes in intracellular calcium flux and pH, (2) the activation of protein kinase C, (3) an increase in intracellular levels of cyclic AMP, and (4) activation of the phosphatidyl inositol pathways. Bombesin and related peptides stimulate a net input of Na+ by 3T3 fibroblasts via a Na+/H+ channel, causing cytoplasmic alkalization.23 This is accompanied by a rapid mobilization of Ca2+ from intracellular stores, leading to a transient increase in intracellular Ca2+ concentrations and an efflux of ions via a Ca2+-ATPase.24 Inositol triphosphate (IP3) is able to act as a second messenger for mitogens that stimulate Ca2+ efflux and phosphoinositol turnover as a result of phospholipase C activation. Bombesin/GRP have been shown to cause increased phospho-inositol metabolism in 3T3 cells, leading to the formation of IP3.25 Both bradykinin and vasopressin also cause rapid increase in intracellular Ca2+.13
Fetal and Neonatal Development of the Exocrine Pancreas
Published in Jean Morisset, Travis E. Solomon, Growth of the Gastrointestinal Tract: Gastrointestinal Hormones and Growth Factors, 2017
Emanuel Lebenthal, Ying-kit Leung
Secretagogues such as CCK and carbachol act by first binding to specific receptors on the surface of the acinar cells. After binding, a series of events collectively termed “stimulus-secretion coupling” take place which finally result in secretion of enzymes from the acinar cells by exocytosis. Pancreatic exocrine secretion is stimulated by secretagogues that act primarily through either the adenylate cyclase system (secretin and vasoactive intestinal polypeptide) or the phosphatidylinositol pathway (CCK and cholinergic agents). The binding of cholecystoki-nin and cholinergic agents to their respective receptors results in the release of inositol trisphosphate and 1,2-diacylglycerol. Inositol trisphosphate induces calcium mobilization and activates calmodulin-dependent protein kinases. At the same time, 1,2-diacyglycerol activates and translocates protein kinase C from a cytosolic to a membraneous site. Taken together, protein kinase C activation, calcium mobilization and subsequent activation of calmodulin dependent protein kinase are viewed as important intermediary steps leading to secretion by the exocrine pancreas.32
Phosphoinositide Metabolism
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Cyclic esters of inositide phosphates may be produced in animal tissues, in addition to noncyclic products, as a result of phosphoinositide degradation by phospholipase C.122,123 Cyclic inositol trisphosphate and bisphosphate can be generated as products of inositol 1,4,5-trisphosphate metabolism. The possible role of these cyclic phosphate intermediates is unknown, but the cyclic phosphate esters contain a reactive bond that could play some role in phosphoinositide-derived signal transduction.
Hyperoside ameliorates cerebral ischaemic–reperfusion injury by opening the TRPV4 channel in vivo through the IP3-PKC signalling pathway
Published in Pharmaceutical Biology, 2023
Lei Shi, Chenchen Jiang, Hanghang Xu, Jiangping Wu, Jiajun Lu, Yuxiang He, Xiuyun Yin, Zhuo Chen, Di Cao, Xuebin Shen, Xuefeng Hou, Jun Han
Accumulating evidence has shown that TRPV4 activation influences vascular dilation by inducing the production of EDHF, NO or PGI2 (Liu et al. 2021). Similar to previous studies, we also found that Hyp-induced vasodilatation is dependent on EDHF production in an NO- and PGI2-independent manner in endothelial cells from the CBA of IR rats. To further investigate the mechanism by which Hyp affects TRPV4 expression, we focused on IP3 and PKC. IP3-associated and PKC-mediated signalling pathways play a critical role in inducing PGI2- and NO-independent vasodilation. IP3 is an important second messenger that binds to inositol triphosphate receptors on the sarcoplasmic reticulum to cause Ca2+ release and an increase in intracellular Ca2+ concentration (Ivanova et al. 2017). Studies have shown that IP3 activation promotes the opening of TRPV4 channels (Heathcote et al. 2019). PKC induces vasodilation through the EDHF mechanism by activating TRPV4, which plays an important role in regulating vasomotor function (Sonkusare et al. 2014). The results herein showed that the expression of IP3R and PKC was markedly increased by the Hyp treatment, and this effect was reduced by treatment with an IP3R inhibitor (2APB) or an inhibitor of PKC (BisI). Importantly, the effect of Hyp on TRPV4 expression was considerably suppressed by the 2APB and BisI treatment, suggesting that Hyp upregulates TRPV4 expression through the activation of the IP3 and PKC signalling pathways.
Genetic variants of FGFR family associated with height, hypertension, and osteoporosis
Published in Annals of Human Biology, 2023
Hye-Won Cho, Hyun-Seok Jin, Yong-Bin Eom
Additionally, FGFRs were involved in the calcium signalling pathway, which is essential for endothelial control of cardiovascular and osteoclast activity. Calcium signals at myoendothelial projections are a fundamental factor in endothelial control of vascular tone (Wilson et al. 2019). One study demonstrated disruption in calcium signalling mediated by inositol trisphosphate (IP3), which results in release of calcium and creates microdomains that are essential to the balance of vascular function, in hypertensive rats (Yuan et al. 2016; Lin et al. 2019; Wilson et al. 2019). In addition, from the bone homeostasis point of view, it is well-known that calcium is essential for activating proliferation of osteoclast precursors and suppressing the resorption of mature osteoclasts (Kajiya 2012). Calcium homeostasis in bone is monitored by parathyroid hormone (PTH). The parathyroid gland has calcium-sensing membrane receptors, and a low level of calcium releases PTH, followed by stimulation of osteoclasts (Teitelbaum 2000).
Emerging therapeutic targets for retinoblastoma
Published in Expert Opinion on Therapeutic Targets, 2022
Radhika Manukonda, Revu VL Narayana, Swathi Kaliki, Dilip K Mishra, Geeta K Vemuganti
Ca2+ is an abundant intracellular molecule that acts as a second messenger that regulates cell proliferation, gene transcription, and apoptosis. Intracellular calcium homeostasis is critical for cell survival. Any alteration in its equilibrium affects molecular factors and signaling pathways such as Ca2+ channels, transporters, calcium-binding proteins, and Ca2+- adenosine triphosphate (ATP)ases. Altered intracellular calcium levels and signaling pathways cause invasion, tumor metastasis, and favor cell survival [23]. Different research groups have studied the involvement of Ca2+-dependent molecular pathways in Rb tumor progression. Kim et al. elucidated the molecular mechanism of calcium mobilization in human Rb. Intracellular calcium molecules from the internally stored deposits are carried out through the inositol triphosphate (IP3)-dependent pathway via activating M3/M5 muscarinic receptors in the undifferentiated Rb cells [24]. Mergler et al. reported that neoplastic properties in Rb are attributed to Ca2+-dependent signaling pathways. The sensitivity of clinical drug etoposide can be enhanced via upregulation of transient receptor potential cation channel gene expression in etoposide-resistant Wills Eye Research Institute-Retinoblastoma-1 (WERI-Rb1) cells [25]. The above reports suggest that Ca2+ channels/transporters and pumps can serve as potential therapeutic targets of Rb.