Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1993-9-24
pubmed:abstractText
Ins(1,3,4,5)P4 was able to mobilize the entire Ins(1,4,5)P3-sensitive intracellular Ca2+ store in saponin-permeabilized SH-SY5Y human neuroblastoma cells in a concentration-dependent manner, yielding an EC50 value of 2.05 +/- 0.45 microM, compared with 0.14 +/- 0.03 microM for Ins(1,4,5)P3. However, L-Ins(1,3,4,5)P4 [= D-Ins(1,3,5,6)P4] failed to cause mobilization of intracellular Ca2+ at concentrations up to 100 microM. Binding studies using pig cerebellar membranes as a source of both Ins(1,4,5)P3/Ins(1,3,4,5)P4-specific binding sites have revealed a marked contrast in their stereospecificity requirements. Ins(1,4,5)P3-receptors from pig cerebella exhibited stringent stereospecificity, L-Ins(1,4,5)P3 and L-Ins(1,3,4,5)P4 were > 1000-fold weaker, whereas Ins(1,3,4,5)P4 (IC50 762 +/- 15 nM) was only about 40-fold weaker than D-Ins(1,4,5)P3 (IC50 20.7 +/- 9.7 nM) at displacing specific [3H]Ins(1,4,5)P3 binding from an apparently homogeneous Ins(1,4,5)P3 receptor population. In contrast, the Ins(1,3,4,5)P4-binding site exhibited poor stereoselectivity. Ins(1,3,4,5)P4 produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding, with two-site analysis revealing KD values for high- and low-affinity sites of 2.1 +/- 0.5 nM and 918 +/- 161 nM respectively. L-Ins(1,3,4,5)P4 also produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding which was less than 10-fold weaker than with D-Ins(1,3,4,5)P4 (IC50 values for the high- and low-affinity sites of 17.2 +/- 3.7 nM and 3010 +/- 542 nM respectively). Therefore, although L-Ins(1,3,4,5)P4 appears to be a high-affinity Ins(1,3,4,5)P4-binding-site ligand in pig cerebellum, it is a very weak agonist at the Ca(2+)-mobilizing receptors of permeabilized SH-SY5Y cells. We suggest that the ability of D-Ins(1,3,4,5)P4 to access intracellular Ca2+ stores may derive from specific interaction with the Ins(1,4,5)P3- and not the Ins(1,3,4,5)P4-receptor population.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1309941, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1314565, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1327920, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1329895, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1463453, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1645528, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1648669, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1657992, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1659392, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1841939, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-1872818, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2012613, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2163607, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2176465, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2185036, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2193258, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2298819, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2469162, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2767136, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2786414, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2786415, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2788744, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2847317, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-2849060, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-3039991, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-3263119, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-3496245, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-3827851, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-3838314, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-686171, http://linkedlifedata.com/resource/pubmed/commentcorrection/8363572-8381210
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0264-6021
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
294 ( Pt 1)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-4
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Stereoselectivity of Ins(1,3,4,5)P4 recognition sites: implications for the mechanism of the Ins(1,3,4,5)P4-induced Ca2+ mobilization.
pubmed:affiliation
Department of Pharmacology and Therapeutics, University of Leicester, U.K.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't