Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.80811
A. Dumitru, D. Toader, S. Crețoiu, D. Crețoiu, N. Suciu, B. Radu
Breast cancer is the second most common cancer in women and the fifth cause contributing to death due to the cancer condition. It is essential to deeply understand the complex cellular mechanisms leading to this disease. There are multiple connections between calcium homeostasis alterations and breast cancer in the literature, but no consensus links the mechanism to the disease prognosis. Among the cells contributing to the breast cancer are the breast telocytes, which connect through gap junctions to other cells, including cancer cells and myoepithelial cells. Multiple proteins (i.e., voltage-gated calcium channels, transient receptor potential channels, STIM and Orai proteins, ether à go-go potassium channels, calcium-activated potassium channels, calcium-activated chloride channels, muscarinic acetylcholine receptors, etc.) coupled with calcium signaling pathways undergo functional and/or expression changes associated with breast cancer development and progression, and might represent promising pharmacological targets. Unraveling the mechanisms of altered calcium homeostasis in various breast cells due to the cancer condition might contribute to personalized therapeutic approaches.
{"title":"Alterations in Calcium Signaling Pathways in Breast Cancer","authors":"A. Dumitru, D. Toader, S. Crețoiu, D. Crețoiu, N. Suciu, B. Radu","doi":"10.5772/INTECHOPEN.80811","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.80811","url":null,"abstract":"Breast cancer is the second most common cancer in women and the fifth cause contributing to death due to the cancer condition. It is essential to deeply understand the complex cellular mechanisms leading to this disease. There are multiple connections between calcium homeostasis alterations and breast cancer in the literature, but no consensus links the mechanism to the disease prognosis. Among the cells contributing to the breast cancer are the breast telocytes, which connect through gap junctions to other cells, including cancer cells and myoepithelial cells. Multiple proteins (i.e., voltage-gated calcium channels, transient receptor potential channels, STIM and Orai proteins, ether à go-go potassium channels, calcium-activated potassium channels, calcium-activated chloride channels, muscarinic acetylcholine receptors, etc.) coupled with calcium signaling pathways undergo functional and/or expression changes associated with breast cancer development and progression, and might represent promising pharmacological targets. Unraveling the mechanisms of altered calcium homeostasis in various breast cells due to the cancer condition might contribute to personalized therapeutic approaches.","PeriodicalId":9411,"journal":{"name":"Calcium and Signal Transduction","volume":"163 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74908627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.78546
D. Dominguez
Calcium (Ca 2+ ) functions as a universal messenger in eukaryotes and regulates many intracellular processes such as cell division and gene expression. However, the physi- ological role of Ca 2+ in prokaryotic cells remains unclear. Indirect evidence suggests that Ca 2+ is involved in a wide variety of bacterial cellular processes including membrane transport mechanisms (channels, primary and secondary transporters), chemotaxis, cell division and cell differentiation processes such as sporulation and heterocyst formation. In addition, Ca 2+ signaling has been implicated in various stages of bacterial infections and host-pathogen interactions. The most significant discovery is that similar to eukary - otic cells, bacteria always maintain very low cytosolic free Ca 2+ , even in the presence of millimolar extracellular Ca 2+ . Furthermore, Ca 2+ transients are produced in response to stimuli by several agents. Transport systems, which may be involved in Ca 2+ homeostasis are present in bacteria but none of these have been examined critically. Ca 2+ -binding proteins have also been identified, including proteins with EF motifs but their role as intracellular Ca 2+ targets is elusive. Genomic studies indicate that changes in intracellular Ca 2+ up and downregulate hundreds of genes and proteins suggesting a physiological role. This chapter presents an overview of the role of Ca 2+ in prokaryotes summarizing recent developments.
{"title":"Calcium Signaling in Prokaryotes","authors":"D. Dominguez","doi":"10.5772/INTECHOPEN.78546","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78546","url":null,"abstract":"Calcium (Ca 2+ ) functions as a universal messenger in eukaryotes and regulates many intracellular processes such as cell division and gene expression. However, the physi- ological role of Ca 2+ in prokaryotic cells remains unclear. Indirect evidence suggests that Ca 2+ is involved in a wide variety of bacterial cellular processes including membrane transport mechanisms (channels, primary and secondary transporters), chemotaxis, cell division and cell differentiation processes such as sporulation and heterocyst formation. In addition, Ca 2+ signaling has been implicated in various stages of bacterial infections and host-pathogen interactions. The most significant discovery is that similar to eukary - otic cells, bacteria always maintain very low cytosolic free Ca 2+ , even in the presence of millimolar extracellular Ca 2+ . Furthermore, Ca 2+ transients are produced in response to stimuli by several agents. Transport systems, which may be involved in Ca 2+ homeostasis are present in bacteria but none of these have been examined critically. Ca 2+ -binding proteins have also been identified, including proteins with EF motifs but their role as intracellular Ca 2+ targets is elusive. Genomic studies indicate that changes in intracellular Ca 2+ up and downregulate hundreds of genes and proteins suggesting a physiological role. This chapter presents an overview of the role of Ca 2+ in prokaryotes summarizing recent developments.","PeriodicalId":9411,"journal":{"name":"Calcium and Signal Transduction","volume":"65 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88092182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.78941
I. Farcasanu, C. Popa, L. Ruta
Despite constant efforts to maintain a clean environment, heavy metal pollution contin - ues to raise challenges to the industrialized world. Exposure to heavy metals is detrimen tal to living organisms, and it is of utmost importance that cells find rapid and efficient ways to respond to and eventually adapt to surplus metals for survival under severe stress. This chapter focuses on the attempts done so far to elucidate the calcium-mediated response to heavy metal stress using the model organism Saccharomyces cerevisiae . The possibilities to record the transient elevations of calcium within yeast cells concomitantly with the heavy metal exposure are presented, and the limitations imposed by interfer ence between calcium and heavy metals are discussed. Ca 2+ influx and mating.
{"title":"Calcium and Cell Response to Heavy Metals: Can Yeast Provide an Answer?","authors":"I. Farcasanu, C. Popa, L. Ruta","doi":"10.5772/INTECHOPEN.78941","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78941","url":null,"abstract":"Despite constant efforts to maintain a clean environment, heavy metal pollution contin - ues to raise challenges to the industrialized world. Exposure to heavy metals is detrimen tal to living organisms, and it is of utmost importance that cells find rapid and efficient ways to respond to and eventually adapt to surplus metals for survival under severe stress. This chapter focuses on the attempts done so far to elucidate the calcium-mediated response to heavy metal stress using the model organism Saccharomyces cerevisiae . The possibilities to record the transient elevations of calcium within yeast cells concomitantly with the heavy metal exposure are presented, and the limitations imposed by interfer ence between calcium and heavy metals are discussed. Ca 2+ influx and mating.","PeriodicalId":9411,"journal":{"name":"Calcium and Signal Transduction","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90069636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.79097
P. Kotova, O. A. Rogachevskaja, M. Bystrova, E. N. Kochkina, D. S. Ivashin, S. Kolesnikov
Mesenchymal stromal cells (MSCs) from different sources represent a heterogeneous population of proliferating non-differentiated cells that contain multipotent stem cells capable of originating a variety of mesenchymal cell lineages. By using Ca 2+ imaging and the Ca 2+ dye Fluo -4 , we studied MSCs from the human adipose tissue and examined Ca 2+ signaling initiated by a variety of GPCR ligands, focusing primarily on adrenergic and purinergic agonists. Being characterized by a relative change of Fluo -4 fluorescence, ago-nist-induced Ca 2+ responses were generated in an “all-or-nothing” fashion. Specifically, at relatively low doses, agonists elicited undetectable responses but initiated quite simi- lar Ca 2+ transients at all concentrations above the threshold. The inhibitory analysis and Ca 2+ /IP 3 uncaging pointed at the phosphoinositide cascade as a pivotal pathway responsible for agonist transduction and implicated Ca 2+ -induced Ca 2+ release (CICR) in shaping agonists-dependent Ca 2+ signals. Altogether, our data suggest that agonist transduction in MSCs includes two fundamentally different stages: an agonist initially triggers a local, gradual, and relatively small Ca 2+ signal, which next stimulates CICR to accomplish transduction with a large and global Ca 2+ transient. By involving the trigger-like mechanism CICR, a cell is capable of generating Ca 2+ responses of virtually universal shape and magnitude at different agonist concentrations above the threshold.
{"title":"Calcium Signaling Initiated by Agonists in Mesenchymal Stromal Cells from the Human Adipose Tissue","authors":"P. Kotova, O. A. Rogachevskaja, M. Bystrova, E. N. Kochkina, D. S. Ivashin, S. Kolesnikov","doi":"10.5772/INTECHOPEN.79097","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79097","url":null,"abstract":"Mesenchymal stromal cells (MSCs) from different sources represent a heterogeneous population of proliferating non-differentiated cells that contain multipotent stem cells capable of originating a variety of mesenchymal cell lineages. By using Ca 2+ imaging and the Ca 2+ dye Fluo -4 , we studied MSCs from the human adipose tissue and examined Ca 2+ signaling initiated by a variety of GPCR ligands, focusing primarily on adrenergic and purinergic agonists. Being characterized by a relative change of Fluo -4 fluorescence, ago-nist-induced Ca 2+ responses were generated in an “all-or-nothing” fashion. Specifically, at relatively low doses, agonists elicited undetectable responses but initiated quite simi- lar Ca 2+ transients at all concentrations above the threshold. The inhibitory analysis and Ca 2+ /IP 3 uncaging pointed at the phosphoinositide cascade as a pivotal pathway responsible for agonist transduction and implicated Ca 2+ -induced Ca 2+ release (CICR) in shaping agonists-dependent Ca 2+ signals. Altogether, our data suggest that agonist transduction in MSCs includes two fundamentally different stages: an agonist initially triggers a local, gradual, and relatively small Ca 2+ signal, which next stimulates CICR to accomplish transduction with a large and global Ca 2+ transient. By involving the trigger-like mechanism CICR, a cell is capable of generating Ca 2+ responses of virtually universal shape and magnitude at different agonist concentrations above the threshold.","PeriodicalId":9411,"journal":{"name":"Calcium and Signal Transduction","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76854359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.78587
F. Martin-Romero, Carlos Pascual-Caro, Aida M. Lopez-Guerrero, Noelia Espinosa-Bermejo, Eulalia Pozo‐Guisado
STIM1 and ORAI1 proteins are regulators of intracellular Ca 2+ mobilization. This Ca 2+ mobilization is essential to shape Ca 2+ signaling in eukaryotic cells. STIM1 is a transmembrane protein located at the endoplasmic reticulum, where it acts as an intraluminal Ca 2+ sensor. The transient drop of intraluminal Ca 2+ concentration triggers STIM1 activation, which relocates to plasma membrane-endoplasmic reticulum junctions to bind and acti- vate ORAI1, a plasma membrane Ca 2+ channel. Thus, the Ca 2+ influx pathway mediated by STIM1/ORAI1 is termed store-operated Ca 2+ entry (SOCE). STIM and ORAI proteins are also involved in non-SOCE Ca 2+ influx pathways, as we discuss here. In this chapter, we review the current knowledge regarding the role of SOCE, STIM1, and ORAI1 in cell signaling, with special focus on the modulation of the activity of kinases, phosphatases, and transcription factors that are strongly influenced by the extracellular Ca 2+ influx mediated by these regulators. Palmitate induces ER calcium
{"title":"Regulation of Calcium Signaling by STIM1 and ORAI1","authors":"F. Martin-Romero, Carlos Pascual-Caro, Aida M. Lopez-Guerrero, Noelia Espinosa-Bermejo, Eulalia Pozo‐Guisado","doi":"10.5772/INTECHOPEN.78587","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78587","url":null,"abstract":"STIM1 and ORAI1 proteins are regulators of intracellular Ca 2+ mobilization. This Ca 2+ mobilization is essential to shape Ca 2+ signaling in eukaryotic cells. STIM1 is a transmembrane protein located at the endoplasmic reticulum, where it acts as an intraluminal Ca 2+ sensor. The transient drop of intraluminal Ca 2+ concentration triggers STIM1 activation, which relocates to plasma membrane-endoplasmic reticulum junctions to bind and acti- vate ORAI1, a plasma membrane Ca 2+ channel. Thus, the Ca 2+ influx pathway mediated by STIM1/ORAI1 is termed store-operated Ca 2+ entry (SOCE). STIM and ORAI proteins are also involved in non-SOCE Ca 2+ influx pathways, as we discuss here. In this chapter, we review the current knowledge regarding the role of SOCE, STIM1, and ORAI1 in cell signaling, with special focus on the modulation of the activity of kinases, phosphatases, and transcription factors that are strongly influenced by the extracellular Ca 2+ influx mediated by these regulators. Palmitate induces ER calcium","PeriodicalId":9411,"journal":{"name":"Calcium and Signal Transduction","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90718242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.79897
R. Wei, S. Lunn, S. Gust, P. Kerr, F. Plane
Maintenance of adequate blood flow to tissues and organs requires that endothelial cells dynamically respond in a stimulus-specific manner to elicit appropriate changes in smooth muscle contractility and thus, arterial diameter. Endothelial cells can be stimu- lated directly by increases in blood flow and by humoral factors acting on surface receptors, as well as through flux of second messengers from smooth muscle cells activated by release of neurotransmitters from perivascular nerves. The ability of endothelial cells to generate stimulus-specific responses to these diverse inputs is facilitated by organization of ion channels and signaling proteins into microdomains that permit finely-tuned, spatially-restricted Ca 2+ events to differentially activate key effectors such as nitric oxide (NO) synthase and Ca 2+ -activated K + (K Ca ) channels. NO is a diffusible mediator which acts locally to cause vasodilation. Opening of K Ca channels causes hyperpolarization of the endothelial membrane potential which spreads to surrounding smooth muscle cells to also cause local vasodilation. However, once initiated, hyperpolarization also spreads longitudinally through the endothelium to effect coordinated changes in blood flow within multiple arterial segments. Thus, the signaling pathways activated by a particular stimulus determine whether it ’ s effects on arterial diameter are localized or can impact blood flow at the level of the vascular bed. by increases in shear stress. Shear stress-evoked Ca 2+ influx through TRPV4 channels on the luminal surface of endothelial cells leads to spatially-restricted Ca 2+ sparklets within a signaling microdomain to selectively activate SK ca channels and endothelial NOS (eNOS).
{"title":"The Endothelium: The Vascular Information Exchange","authors":"R. Wei, S. Lunn, S. Gust, P. Kerr, F. Plane","doi":"10.5772/INTECHOPEN.79897","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79897","url":null,"abstract":"Maintenance of adequate blood flow to tissues and organs requires that endothelial cells dynamically respond in a stimulus-specific manner to elicit appropriate changes in smooth muscle contractility and thus, arterial diameter. Endothelial cells can be stimu- lated directly by increases in blood flow and by humoral factors acting on surface receptors, as well as through flux of second messengers from smooth muscle cells activated by release of neurotransmitters from perivascular nerves. The ability of endothelial cells to generate stimulus-specific responses to these diverse inputs is facilitated by organization of ion channels and signaling proteins into microdomains that permit finely-tuned, spatially-restricted Ca 2+ events to differentially activate key effectors such as nitric oxide (NO) synthase and Ca 2+ -activated K + (K Ca ) channels. NO is a diffusible mediator which acts locally to cause vasodilation. Opening of K Ca channels causes hyperpolarization of the endothelial membrane potential which spreads to surrounding smooth muscle cells to also cause local vasodilation. However, once initiated, hyperpolarization also spreads longitudinally through the endothelium to effect coordinated changes in blood flow within multiple arterial segments. Thus, the signaling pathways activated by a particular stimulus determine whether it ’ s effects on arterial diameter are localized or can impact blood flow at the level of the vascular bed. by increases in shear stress. Shear stress-evoked Ca 2+ influx through TRPV4 channels on the luminal surface of endothelial cells leads to spatially-restricted Ca 2+ sparklets within a signaling microdomain to selectively activate SK ca channels and endothelial NOS (eNOS).","PeriodicalId":9411,"journal":{"name":"Calcium and Signal Transduction","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89756612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.79556
Rogelio Salazar-Enciso, Nohemí Camacho-Concha, T. Mesquita, D. Falcón, J. Benitah, A. Gómez, A. Rueda
For decades, the mineralocorticoid receptor (MR) antagonists have been used for the management of cardiovascular diseases; however, the molecular mechanisms involved in their beneficial effects are not fully understood. Recent publications point to the fun - damental role of aldosterone and vascular MR in the regulation of arterial tone, vascular contractility, and cell proliferation. However, the intricate transduction machinery acti - vated by vascular MRs has begun to be revealed with the help of transgenic rodent mod els and novel transcriptional analysis approaches. Specifically, in this chapter, we review and discuss the most recent contributions about the fine-tuning that the MR exerts on the expression and function of ion channels that participate in calcium handling of vascular cells and the therapeutic implications for hypertension and cardiovascular diseases.
{"title":"Mineralocorticoid Receptor in Calcium Handling of Vascular Smooth Muscle Cells","authors":"Rogelio Salazar-Enciso, Nohemí Camacho-Concha, T. Mesquita, D. Falcón, J. Benitah, A. Gómez, A. Rueda","doi":"10.5772/INTECHOPEN.79556","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79556","url":null,"abstract":"For decades, the mineralocorticoid receptor (MR) antagonists have been used for the management of cardiovascular diseases; however, the molecular mechanisms involved in their beneficial effects are not fully understood. Recent publications point to the fun - damental role of aldosterone and vascular MR in the regulation of arterial tone, vascular contractility, and cell proliferation. However, the intricate transduction machinery acti - vated by vascular MRs has begun to be revealed with the help of transgenic rodent mod els and novel transcriptional analysis approaches. Specifically, in this chapter, we review and discuss the most recent contributions about the fine-tuning that the MR exerts on the expression and function of ion channels that participate in calcium handling of vascular cells and the therapeutic implications for hypertension and cardiovascular diseases.","PeriodicalId":9411,"journal":{"name":"Calcium and Signal Transduction","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83338689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-24DOI: 10.5772/INTECHOPEN.78370
W. Zhong, N. Darmani
Cisplatin-like chemotherapeutics cause vomiting via calcium (Ca 2+ )-dependent release of multiple neurotransmitters/mediators (dopamine, serotonin, substance P, prosta - glandins and leukotrienes) from the gastrointestinal enterochromaffin cells and/or the brainstem. Intracellular Ca 2+ signaling is triggered by activation of diverse emetic recep tors (including neurokininergic NK 1 , serotonergic 5-HT 3 , dopaminergic D 2 , cholinergic M 1 , or histaminergic H 1 ) , whose stimulation in vomit-competent species evokes emesis. Other emetogens such as cisplatin, rotavirus NSP4 protein, and bacterial toxins can also induce intracellular Ca 2+ elevation. Our findings demonstrate that application of the L-type Ca 2+ channel (LTCC) agonist FPL 64176 and the intracellular Ca 2+ mobilizing agent thapsigargin (a sarco/endoplasmic reticulum Ca 2+ -ATPase inhibitor) cause vomiting in the least shrew. On the other hand, blockade of LTCCs by corresponding antagonists (nifedipine or amlodipine) not only provide broad-spectrum antiemetic efficacy against diverse agents that specifically activate emetogenic receptors such as 5-HT 3 , NK 1 , D 2 , and M 1 receptors, but can also potentiate the antiemetic efficacy of palonosetron against the nonspecific emetogen, cisplatin. In this review, we will provide an overview of Ca 2+ involvement in the emetic process; discuss the relationship between Ca 2+ signaling and the prevailing therapeutics in control of vomiting; highlight the current evidence for Ca 2+ signaling blockers/inhibitors in suppressing emetic behavior and also draw attention to the clinical benefits of Ca 2+ -signaling blockers/inhibitors for the treatment of nausea and vomiting. (10 mg/kg, i.p.), the and non-selective 5-HT agonist 5-HT (5 mg/kg, i.p.), the peripherally/centrally-acting and more selective 5-HT 3 R agonist (5 mg/kg, i.p.), the D 2 R-preferring agonist quinpirole (2 mg/kg, i.p.), the non-selective dopamine D 2 R agonist apomorphine (2 mg/kg, i.p.), the nonselective cho linergic agonist pilocarpine (2 mg/kg, i.p.), the M 1 -preferring cholinergic agonist McN-A343 (2 mg/kg, i.p.), and the selective neurokinin NK 1 R agonist GR73632 (5 mg/kg, i.p.). The vomiting behavior was recorded for 30 min. Our results suggest that both amlodipine and nifedipine act by suppressing the influx of extracellular Ca 2+ , thereby delay the onset as well as protect ing least shrews from vomiting, further supporting our proposed Ca 2+ hypothesis of emesis. totally dependent upon G i/o [144]. These signaling effects were totally inhibited by various specific CysLT1-receptor antagonists, and CysLT1 antago nists the P2Y agonist-induced activation of phospholipase C and intracellular
{"title":"Role of Calcium in Vomiting","authors":"W. Zhong, N. Darmani","doi":"10.5772/INTECHOPEN.78370","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78370","url":null,"abstract":"Cisplatin-like chemotherapeutics cause vomiting via calcium (Ca 2+ )-dependent release of multiple neurotransmitters/mediators (dopamine, serotonin, substance P, prosta - glandins and leukotrienes) from the gastrointestinal enterochromaffin cells and/or the brainstem. Intracellular Ca 2+ signaling is triggered by activation of diverse emetic recep tors (including neurokininergic NK 1 , serotonergic 5-HT 3 , dopaminergic D 2 , cholinergic M 1 , or histaminergic H 1 ) , whose stimulation in vomit-competent species evokes emesis. Other emetogens such as cisplatin, rotavirus NSP4 protein, and bacterial toxins can also induce intracellular Ca 2+ elevation. Our findings demonstrate that application of the L-type Ca 2+ channel (LTCC) agonist FPL 64176 and the intracellular Ca 2+ mobilizing agent thapsigargin (a sarco/endoplasmic reticulum Ca 2+ -ATPase inhibitor) cause vomiting in the least shrew. On the other hand, blockade of LTCCs by corresponding antagonists (nifedipine or amlodipine) not only provide broad-spectrum antiemetic efficacy against diverse agents that specifically activate emetogenic receptors such as 5-HT 3 , NK 1 , D 2 , and M 1 receptors, but can also potentiate the antiemetic efficacy of palonosetron against the nonspecific emetogen, cisplatin. In this review, we will provide an overview of Ca 2+ involvement in the emetic process; discuss the relationship between Ca 2+ signaling and the prevailing therapeutics in control of vomiting; highlight the current evidence for Ca 2+ signaling blockers/inhibitors in suppressing emetic behavior and also draw attention to the clinical benefits of Ca 2+ -signaling blockers/inhibitors for the treatment of nausea and vomiting. (10 mg/kg, i.p.), the and non-selective 5-HT agonist 5-HT (5 mg/kg, i.p.), the peripherally/centrally-acting and more selective 5-HT 3 R agonist (5 mg/kg, i.p.), the D 2 R-preferring agonist quinpirole (2 mg/kg, i.p.), the non-selective dopamine D 2 R agonist apomorphine (2 mg/kg, i.p.), the nonselective cho linergic agonist pilocarpine (2 mg/kg, i.p.), the M 1 -preferring cholinergic agonist McN-A343 (2 mg/kg, i.p.), and the selective neurokinin NK 1 R agonist GR73632 (5 mg/kg, i.p.). The vomiting behavior was recorded for 30 min. Our results suggest that both amlodipine and nifedipine act by suppressing the influx of extracellular Ca 2+ , thereby delay the onset as well as protect ing least shrews from vomiting, further supporting our proposed Ca 2+ hypothesis of emesis. totally dependent upon G i/o [144]. These signaling effects were totally inhibited by various specific CysLT1-receptor antagonists, and CysLT1 antago nists the P2Y agonist-induced activation of phospholipase C and intracellular","PeriodicalId":9411,"journal":{"name":"Calcium and Signal Transduction","volume":"209 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80581524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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