Linked Life Data

17264160

Source:http://linkedlifedata.com/resource/pubmed/id/17264160

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-5-1
pubmed:abstractText
Benzene polyphosphates containing phosphate groups on one ring are Ins(1,4,5)P3 5-phosphatase inhibitors when evaluated against type-I Ins(1,4,5)P3 5-phosphatase. A novel biphenyl derivative, biphenyl 2,3',4,5',6-pentakisphosphate, with five phosphate groups on two rings was synthesized: It inhibited the activity of two inositol 5-phosphatases: type I and SHIP2 with Ins(1,3,4,5)P4 as substrate. The inhibition was competitive with respect to the substrate. IC50 value measured in rat hepatocytes, which contains the native Ins(1,4,5)P3 5-phosphatase, was in the micromolar range at 1.0 microM Ins(1,4,5)P3 as substrate. Biphenyl 2,3',4,5',6-pentakisphosphate did not affect the activity of Ins(1,4,5)P3 3-kinase A in the 5-100 microM range. Surprisingly, experimental evidence supports an effect of biphenyl 2,3',4,5',6-pentakisphosphate at the level of the Ins(1,4,5)P3 receptor. Finally, when injected into rat hepatocytes, the analog affected the frequency of Ca2+ oscillations in a positive or negative way depending on its concentration. At very high concentrations of the analog, Ca2+ oscillations were even suppressed. These data were interpreted as a dual effect of the biphenyl 2,3',4,5',6-pentakisphosphate on cytosolic [Ca2+] increases: an activation effect through an increase in Ins(1,4,5)P3 level via Ins(1,4,5)P3 5-phosphatase inhibition and an inhibitory effect, which was exerted directly on the Ins(1,4,5)P3 receptor. Thus, our data show for the first time that the frequency of Ca2+ oscillations in response to a Ca2+-mobilizing agonist can be controlled by inhibitors of type-I Ins(1,4,5)P3 5-phosphatase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1481-91
pubmed:dateRevised
2007-8-13
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Biphenyl 2,3',4,5',6-pentakisphosphate, a novel inositol polyphosphate surrogate, modulates Ca2+ responses in rat hepatocytes.
pubmed:affiliation
Institut de Recherche Interdisciplinaire (IRIBHM), Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't