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. 1990 Aug 15;270(1):227–232. doi: 10.1042/bj2700227

Liver inositol, 1,4,5-trisphosphate-binding sites are the Ca2(+)-mobilizing receptors.

D L Nunn 1, C W Taylor 1
PMCID: PMC1131702  PMID: 2168702

Abstract

Ins(1,4,5)P3 is the intracellular messenger that in many cells mediates the effects of Ca2(+)-mobilizing receptors on intracellular Ca2+ stores. An Ins(1,4,5)P3 receptor from cerebellum has been purified and functionally reconstituted, but the relationship between this protein and the high-affinity Ins(1,4,5)P3-binding sites of peripheral tissues is unclear. We compared the Ins(1,4,5)P3-binding sites of liver and cerebellum by measuring inhibition of specific Ins(1,4,[32P]5)P3 binding by various ligands under equilibrium conditions, and find that each ligand binds with similar affinity in the two tissues. Earlier studies in which Ins(1,4,5)P3 binding and Ca2+ mobilization were measured under different conditions demonstrated large differences between KD values for binding and EC50 values (concn. giving half-maximal effect) for Ca2+ release. We show here that, when measured under identical conditions, KD and EC50 values for four agonists are similar. Schild analysis of inhibition of Ins(1,4,5)P3 binding by ATP demonstrates a competitive interaction between the two at the liver Ins(1,4,5)P3-binding site, and this partly accounts for earlier discrepancies in binding and Ca2(+)-release data. We conclude that the high-affinity Ins(1,4,5)P3-binding site of hepatocytes is likely to be the receptor that mediates Ca2+ mobilization, and that this receptor is at present indistinguishable from that in cerebellum.

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Selected References

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