The Novel Ins(1,4,5)P3 Analog 3-Amino-3-deoxy-Ins(1,4,5)P3: A pH-Dependent Ins(1,4,5)P3 Receptor Partial Agonist in SH-SY5Y Neuroblastoma Cells

Alan P. Kozikowski, Abdul H. Fauq, Robert A. Wilcox, R. A.John Challiss, Stefan R. Nahorski

Research output: Contribution to journalComment/debate

Abstract

We have synthesized the first amino-substituted inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] analogue, d-3-amino-3-deoxy-myo-Ins(1,4,5)P3 (9). Although 9 is a full agonist at the Ca2+ mobilizing Ins(1,4,5)P3 receptor at pH 7.2 and 7.6, it is apparently a high intrinsic activity partial agonist at pH 6.8, releasing only 80% of the Ins(1,4,5)P3-sensitive Ca2+ stores of SH-SY5Y cells. Additionally, 9 was able to fully displace [3H]Ins(1,4,5)P3 from binding sites in rat cerebellum membranes at both pH 6.8 and 7.6, indicating a full interaction with the Ins(1,4,5)P3 receptor. The activity displayed by this amino analogue is unexpected and may be indicative of a pH-dependent conformational change in the amino acid residues comprising the Ins(1,4,5)P3 binding site.

Original languageEnglish (US)
Pages (from-to)868-872
Number of pages5
JournalJournal of medicinal chemistry
Volume37
Issue number6
DOIs
StatePublished - Mar 1 1994

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'The Novel Ins(1,4,5)P<sub>3</sub> Analog 3-Amino-3-deoxy-Ins(1,4,5)P<sub>3</sub>: A pH-Dependent Ins(1,4,5)P<sub>3</sub> Receptor Partial Agonist in SH-SY5Y Neuroblastoma Cells'. Together they form a unique fingerprint.

  • Cite this