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Inositol hexakisphosphate binding sites in rat heart and brain
Author(s) -
Rowley Kevin G.,
Gundlach Andrew L.,
Cincotta Marion,
Louis William J.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15582.x
Subject(s) - inositol , inositol phosphate , radioligand , binding site , receptor , stimulation , chemistry , ventricle , biology , medicine , stereochemistry , endocrinology , biochemistry
1 . Inositol 1,4,5‐trisphosphate (Ins(1,4,5)P 3 ) and inositol hexakisphosphate (InsP 6 ) are produced in response to stimulation of cardiac α 1 ‐adrenoceptors. While the role of Ins(1,4,5)P 3 and Ins(1,4,5)P 3 receptors is well‐defined in many tissues including brain, the functional role of the putative InsP 6 ‐InsP 6 receptor system in cardiac function is less clear. Using quantitative autoradiography, this study examined the characteristics and regional localization of [ 3 H]‐InsP 6 binding sites in rat heart and compared the affinity of a range of inositol polyphosphates for [ 3 H]‐InsP 6 and [ 3 H]‐Ins(1,4,5)P 3 binding sites in heart and brain. 2 . [ 3 H]‐InsP 6 bound to a single, high affinity site in sections of rat heart ( K D ranging from 22 ± 1.9 nM in right atria to 35 ± 2.6 nM in the interventricular septum, n = 7). The maximal number of binding sites ( B max ) ranged from 5.1 ± 0.48 to 12 ± 1.8 pmol mg −1 protein in left atrium and left ventricle, respectively. Inositol phosphates inhibited binding of [ 3 H]‐InsP 6 with the order of potency: InsP 6 > Ins(1,4,5)PS 3 > inositol 1,3,4,5‐tetrakisphosphate ≥ inositol pentakisphosphate > Ins(1,4,5)P 3 > > inositol mono‐ and bisphosphates, consistent with the labelling of an InsP 6 binding site. 3 . The Ins(1,4,5)P 3 analogue, Ins(1,4,5)PS 3 , originally investigated as a putative selective radioligand for the Ins(1,4,5)P 3 receptor, was a potent inhibitor of [ 3 H]‐InsP 6 binding in all heart regions ( K I = 170–260 nM). The K I of Ins(1,4,5)PS 3 for the inhibition of [ 3 H]‐Ins(1,4,5)P 3 binding in rat brain (60–220 nM) was similar to that observed for the inhibition of [ 3 H]‐InsP 6 binding in heart, suggesting that Ins(1,4,5)PS 3 is not a specific ligand for either Ins(1,4,5)P 3 or InsP 6 receptor binding sites. 4 . Previous studies have detected [ 3 H]‐InsP 6 binding in mitochondrial and sarcoplasmic reticulum fractions of heart and links between InsP 6 and cardiac mitochondrial Ca 2+ regulation have been proposed, suggesting further studies are warranted to determine the functional role(s) of InsP 6 and InsP 6 receptor binding sites in cardiac tissue.