Linked Life Data

2213562

Source:http://linkedlifedata.com/resource/pubmed/id/2213562

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-11-21
pubmed:abstractText
Serotonin (5-HT)-induced changes in the levels of intracellular Ca++ were analyzed in human platelets, using the Ca+(+)-sensitive dye 1-(2-(5'-carboxyoxazol-2'-yl)-6-aminobenzofuran-5-oxy)-2-(2' -amino-5'- methylphenox)-ethane-N,N,N',N'-tetraacetic acid, pentaacetoxymethyl ester, to investigate the regulation of 5-HT2 receptor function. Serotonin mobilized intracellular Ca++ in a dose-dependent fashion from basal level of 98 +/- 2.7 and up to 211 +/- 5.8 nM with an EC50 value for 5-HT of 0.2 microM. Ketanserin, a 5-HT2 antagonist, reversed the 5-HT (10 microM)-induced Ca++ increase in a dose-dependent manner with an IC50 value of 2 nM. An initial treatment with 10 microM 5-HT abolished the response to a second treatment with 100 microM 5-HT, suggesting that 5-HT evoked an acute desensitization of 5-HT2 receptors in human platelets. Mezerein and phorbol 12-myristate 13-acetate, activators of protein kinase C, inhibited 5-HT-stimulated inositol monophosphate accumulation with IC50 values of 3 and 10 nM, respectively. Furthermore, a protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride prevented the protein kinase C activator-induced inhibition against 5-HT-mediated inositol monophosphate accumulation. Mezerein also inhibited 5-HT (10 microM)-mediated Ca++ release with an IC50 value of 3 nM. 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride prevented the inhibition by mezerein of the 5-HT-stimulated Ca++ increase. Moreover, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride by itself enhanced the Ca++ spike induced by 100 microM 5-HT, the plateau phase induced by 10 microM 5-HT and the second response to 5-HT. These findings suggest that 5-HT2 receptor activation mobilizes intracellular Ca++ in human platelets and that this receptor may be desensitized acutely by a protein kinase C mediated feedback system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
255
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
305-11
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Serotonin-induced acute desensitization of serotonin2 receptors in human platelets via a mechanism involving protein kinase C.
pubmed:affiliation
Division of Mental Disorder Research, National Institute of Neuroscience, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't