Linked Life Data

7971730

Source:http://linkedlifedata.com/resource/pubmed/id/7971730

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-11-28
pubmed:abstractText
Receptor-mediated phosphoinositide signaling pathway which generates a variety of second messengers is regulated by intracellular free Ca2+ concentrations. Since toxic metal cations like Pb2+ are known to alter Ca(2+)-dependent processes, the present study was initiated to study the effects of Pb2+ on inositol 1,4,5-trisphosphate (InsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4) receptor binding and InsP3-mediated Ca(2+)-release. Rat cerebellar membrane and microsomal fractions were incubated with various concentrations of Pb2+ (0.01-100 microM). Pb2+ significantly stimulated [3H]-InsP3 and [3H]-InsP4 receptor binding (EC50 22.7 and 13.5 microM respectively) as a function of metal concentrations. However, InsP3-mediated Ca2+ release, determined by measuring the changes in fluorescence intensity of Fura-2, was significantly inhibited by varying concentrations of Pb2+. Re-uptake of Ca2+ into the microsomes was also inhibited by Pb2+. A significant inhibition of microsomal Ca(2+)-pump by micromolar concentration of Pb2+ was also observed. ATP at 5-1000 microM concentration range inhibited [3H]-InsP3 and [3H]-InsP4 binding to the specific receptors. [3H]-InsP4 receptor binding was more sensitive to ATP inhibition as compared to [3H]-InsP3 receptor binding. Furthermore, varying concentrations of ATP also inhibited Pb(2+)-mediated increase in [3H]-InsP3 and [3H]-InsP4 receptor binding. The kinetic analysis of ATP effect on Pb(2+)-stimulated [3H]-InsP4 receptor binding revealed non-competitive type of interaction. The results of the present study suggest that Pb2+ may be increasing the binding of [3H]-InsP3 and [3H]-InsP4 to the specific receptors by modulating the conformation of the receptor sites. ATP may be playing a protective role in Pb2+ induced alteration of the receptor sites.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0901-9928
pubmed:author
pubmed:issnType
Print
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Lead alters inositol polyphosphate receptor activities: protection by ATP.
pubmed:affiliation
Department of Neurology, University of Mississippi Medical Center, Jackson 39216.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.