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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6 Pt 1
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pubmed:dateCreated |
1989-1-26
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pubmed:abstractText |
Although peptidoleukotriene (LTC4, LTD4) receptors have been characterized by radioligand binding studies, pathways of transmembrane signaling by activated leukotriene receptors remain obscure. We employed [3H]LTD4 binding studies and fluorescent measurements of intracellular Ca2+ concentration ([Ca2+]) and pH to identify LTD4 receptors and mechanisms of transmembrane signaling in cultured human mesangial cells. Mesangial cells expressed a single class of saturable, specific binding sites for [3H]LTD4. Kinetic, competition, and saturation analyses gave an average KD of approximately 12.0 nM with a Bmax of 987 fmol/mg protein. LTC4 competed with high affinity for [3H]LTD4 binding sites, as did LTB4 but with much lower affinity. [3H]LTD4 binding was blocked by a specific LTD4 receptor antagonist, SKF 102922. LTD4 and LTC4 also evoked a rapid (2-3 s), transient increase in intracellular [Ca2+], followed by a second, sustained increase. The transient phase was independent of extracellular Ca2+, whereas the sustained phase was dependent on extracellular Ca2+. Intracellular [Ca2+] was unaffected by LTB4. The LTD4-stimulated Ca2+ transients were dose dependent (1 nM-1 microM) and, similar to [3H]LTD4 binding, Ca2+ transients were inhibited by LTD4 receptor antagonists. We also report evidence that LTD4 affects intracellular pH and activates Na+-H+ exchange. Specifically, LTD4 induced an initial acidification within 1-2 min, followed by net alkalinization at 5 min. Alkalinization was due to activation of an amiloride-inhibitable Na+-H+ exchanger. LTD4 receptors were apparently not coupled to adenylate cyclase or phospholipase A2 as we detected no changes of adenosine 3',5'-cyclic monophosphate (cAMP) or prostanoids. Thus we conclude that [3H]LTD4 binding sites on human mesangial cells are coupled to a Ca2+-signaling system and Na+-H+ exchange. Moreover LTD4, a potent inflammatory mediator, failed to stimulate cAMP or prostaglandin E2/prostaglandin I2, two counterregulatory autacoids that preserve normal mesangial function.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Leukotriene,
http://linkedlifedata.com/resource/pubmed/chemical/SRS-A,
http://linkedlifedata.com/resource/pubmed/chemical/Thromboxane B2
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
255
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C771-80
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2849305-Binding, Competitive,
pubmed-meshheading:2849305-Calcium,
pubmed-meshheading:2849305-Cell Membrane,
pubmed-meshheading:2849305-Cells, Cultured,
pubmed-meshheading:2849305-Cyclic AMP,
pubmed-meshheading:2849305-Glomerular Mesangium,
pubmed-meshheading:2849305-Humans,
pubmed-meshheading:2849305-Hydrogen-Ion Concentration,
pubmed-meshheading:2849305-Kinetics,
pubmed-meshheading:2849305-Prostaglandins,
pubmed-meshheading:2849305-Receptors, Immunologic,
pubmed-meshheading:2849305-Receptors, Leukotriene,
pubmed-meshheading:2849305-SRS-A,
pubmed-meshheading:2849305-Signal Transduction,
pubmed-meshheading:2849305-Thromboxane B2
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pubmed:year |
1988
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pubmed:articleTitle |
Identification and transmembrane signaling of leukotriene D4 receptors in human mesangial cells.
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pubmed:affiliation |
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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