| Two distinct signaling pathways for regulation of spontaneous local Ca2+ release by phospholipase C in airway smooth muscle cells. | |
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MedLine Citation:
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PMID: 17093969 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Spontaneous local Ca(2+) release events have been observed in airway smooth muscle cells (SMCs), but the underlying mechanisms are largely unknown. Considering that each type of SMCs may use its own mechanisms to regulate local Ca(2+) release events, we sought to investigate the signaling pathway for spontaneous local Ca(2+) release events in freshly isolated mouse airway SMCs using a laser scanning confocal microscope. Application of ryanodine to block ryanodine receptors (RyRs) abolished spontaneous local Ca(2+) release events, indicating that these events are RyR-mediated Ca(2+) sparks. Inhibition of inositol 1,4,5-triphosphate receptors (IP(3)Rs) by 2-aminoethoxydiphenyl-borate (2-APB) or xestospongin-C significantly blocked the activity of Ca(2+) sparks. Under patch clamp conditions, dialysis of IP(3) to activate IP(3)Rs increased the activity of local Ca(2+) events in control cells but had no effect in ryanodine-pretreated cells. The RyR agonist caffeine augmented the frequency of Ca(2+) sparks in cells pretreated with and without 2-APB or xestospongin-C. The specific phospholipase C (PLC) blocker U73122 decreased the activity of Ca(2+) sparks and prevented xestospongin-C from producing the inhibitory effect. The protein kinase C (PKC) activator 1-oleoyl-2-acetyl-glycerol or phorbol-12-myristate-13-acetate inhibited Ca(2+) sparks, whereas the PKC inhibitor chelerythrine, PKCvarepsilon inhibitory peptide, or PKCvarepsilon gene knockout produced an opposite effect. Collectively, our data suggest that the basal activation of PLC regulates the activity of RyR-mediated, spontaneous Ca(2+) sparks in airway SMCs through two distinct signaling pathways: a positive IP(3)-IP(3)R pathway and a negative diacylglycerol-PKCvarepsilon pathway. |
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Authors:
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Qing-Hua Liu; Yun-Min Zheng; Yong-Xiao Wang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-11-09 |
Journal Detail:
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Title: Pflügers Archiv : European journal of physiology Volume: 453 ISSN: 0031-6768 ISO Abbreviation: Pflugers Arch. Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2006-12-20 Completed Date: 2007-06-11 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0154720 Medline TA: Pflugers Arch Country: Germany |
Other Details:
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Languages: eng Pagination: 531-41 Citation Subset: IM |
Affiliation:
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Center for Cardiovascular Sciences, Albany Medical College (MC-8), 47 New Scotland Avenue, Albany, NY 12208, USA. wangy@mail.amc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkaloids
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pharmacology Animals Benzophenanthridines / pharmacology Boron Compounds / pharmacology Caffeine / pharmacology Calcium / metabolism* Cells, Cultured Diglycerides / pharmacology Estrenes / pharmacology Inositol 1,4,5-Trisphosphate / metabolism Inositol 1,4,5-Trisphosphate Receptors / antagonists & inhibitors, physiology Macrocyclic Compounds / pharmacology Male Mice Myocytes, Smooth Muscle / drug effects, metabolism* Oxazoles / pharmacology Pyrrolidinones / pharmacology Respiratory System / cytology, drug effects, metabolism Ryanodine / pharmacology Ryanodine Receptor Calcium Release Channel / metabolism, physiology Sarcoplasmic Reticulum / drug effects, metabolism Signal Transduction / drug effects, physiology* Type C Phospholipases / antagonists & inhibitors, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/2-aminoethoxydiphenyl borate; 0/Alkaloids; 0/Benzophenanthridines; 0/Boron Compounds; 0/Diglycerides; 0/Estrenes; 0/Inositol 1,4,5-Trisphosphate Receptors; 0/Macrocyclic Compounds; 0/Oxazoles; 0/Pyrrolidinones; 0/Ryanodine Receptor Calcium Release Channel; 0/xestospongin C; 112648-68-7/1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; 15662-33-6/Ryanodine; 34316-15-9/chelerythrine; 58-08-2/Caffeine; 7440-70-2/Calcium; 85166-31-0/Inositol 1,4,5-Trisphosphate; 86390-77-4/1-oleoyl-2-acetylglycerol; EC 3.1.4.-/Type C Phospholipases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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