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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1995-9-26
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pubmed:abstractText |
Second messenger coupling of the 5-hydroxytryptamine (5-HT)2A receptor endogenous to cultured rat glomerular mesangial cells was studied. 5-HT induced an increase in total inositol phosphate levels (EC50 = 265 +/- 55 nM, maximum stimulation = 150 +/- 23%). That effect was sensitive to antagonists of the 5-HT2A receptor and was insensitive to pertussis toxin at doses that eliminated detectable pertussis toxin substrate, as determined by membrane ADP-ribosylation. Surprisingly, 5-HT also induced an inhibition of forskolin-stimulated cAMP accumulation (55 +/- 6%, IC50 = 5 +/- 3 nM). This effect was competitively antagonized by the 5-HT2A receptor antagonists ketanserin, ritanserin, and spiperone and could be produced by the 5-HT2 receptor agonists alpha-methyl-5-HT (66 +/- 13%, IC50 = 23 +/- 14 nM) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (65 +/- 4%, IC50 = 14 +/- 7 nM). The inhibition of cAMP accumulation occurred in the presence of a number of agents that either stimulate or inhibit protein kinase C activity, arachidonic acid metabolism, or Ca2+ mobilization. In isolated membranes, 5-HT induced a 36 +/- 5% inhibition of adenylyl cyclase activity (IC50 = 8 +/- 4 nM). Inhibition of cAMP accumulation in intact cells and of adenylyl cyclase activity in washed membranes was (> 50%) sensitive to pertussis toxin, implicating Gi alpha or Go alpha subunits in the inhibitory signal. These data suggest that the 5-HT2A receptor can be permissive in its coupling to G proteins and second messengers.
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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/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
230-7
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:7651356-Adenylate Cyclase,
pubmed-meshheading:7651356-Animals,
pubmed-meshheading:7651356-Cells, Cultured,
pubmed-meshheading:7651356-Cyclic AMP,
pubmed-meshheading:7651356-Enzyme Activation,
pubmed-meshheading:7651356-GTP-Binding Proteins,
pubmed-meshheading:7651356-Glomerular Mesangium,
pubmed-meshheading:7651356-Protein Kinase C,
pubmed-meshheading:7651356-Rats,
pubmed-meshheading:7651356-Receptors, Serotonin,
pubmed-meshheading:7651356-Serotonin,
pubmed-meshheading:7651356-Signal Transduction
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pubmed:year |
1995
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pubmed:articleTitle |
5-Hydroxytryptamine2A receptors expressed in rat renal mesangial cells inhibit cyclic AMP accumulation.
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pubmed:affiliation |
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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