Intracellular receptors for inositol 1,4,5-trisphosphate in angiotensin II target tissues

G. Guillemette, T. Balla, A. J. Baukal, A. Spät, K. J. Catt

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Abstract

Many cells (including angiotensin II target cells) respond to external stimuli with accelerated hydrolysis of phosphatidylinositol 4,5-bisphosphate, generating 1,2-diacylglycerol and inositol 1,4,5-trisphosphate, a rapidly diffusible and potent Ca2+-mobilizing factor. Following its production at the plasma membrane level, inositol 1,4,5-trisphosphate is believed to interact with specific sites in the endoplasmic reticulum and triggers the release of stored Ca2+. Specific receptor sites for inositol 1,4,5-trisphosphate were recently identified in the bovine adrenal cortex and have been further characterized in the adrenal cortex and other target tissues. The inositol 1,4,5-trisphosphate-binding sites are saturable and present in low concentration (104 ± 48 fmol/mg protein) and exhibit high affinity for inositol 1,4,5-trisphosphate (K(d) 1.7 ± 0.6 nM). Their ligand specificity is illustrated by their low affinity for inositol 1,4-bisphosphate (K(d) ~ 10-7 M), inositol 1-phosphate and phytic acid (K(d) ~ 10-4 M), fructose 1,6-bisphosphate and 2,3-bisphosphoglycerate (K(d) ~ 10-3 M), with no detectable affinity for inositol 1-phosphate and myo-inositol. These binding sites are distinct from the degradative enzyme, inositol trisphosphate phosphatase, which has a much lower affinity for inositol trisphosphate (K(m) = 17 μM). Furthermore, submicromolar concentrations of inositol 1,4,5-trisphosphate evoked a rapid release of Ca2+ from nonmitochondrial ATP-dependent storage sites in the adrenal cortex. Specific and saturable binding sites for inositol 1,4,5-trisphosphate were also observed in the anterior pituitary (K(d) = 0.87 ± 0.31 nM, B(max) = 14.8 ± 9.0 fmol/mg protein) and in the liver (K(d) = 1.66 ± 0.7 nM, B(max) = 147 ± 24 fmol/mg protein). These data suggest that the binding sites described in this study are specific receptors through which inositol 1,4,5-trisphosphate mobilizes Ca2+ in target tissues for angiontensin II and other calcium-dependent hormones.

Original languageEnglish
Pages (from-to)1010-1015
Number of pages6
JournalJournal of Biological Chemistry
Volume262
Issue number3
Publication statusPublished - May 4 1987

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Guillemette, G., Balla, T., Baukal, A. J., Spät, A., & Catt, K. J. (1987). Intracellular receptors for inositol 1,4,5-trisphosphate in angiotensin II target tissues. Journal of Biological Chemistry, 262(3), 1010-1015.