Complexation of spermine and spermidine by myo-inositol 1,4,5-tris(phosphate) and related compounds: biological significance.
D myo-inositol 1,4,5-tris(phosphate) (Ins(1,4,5)P3) displays a multicoordination site arrangement that allows strong interactions with polycationic species such as the naturally occurring polyamines spermine and spermidine. In the present work, the complexation of these polyamines by Ins(1,4,5)P3 and related compounds was quantitatively investigated. The study was performed in a 0.1 M tetramethylammonium p-toluenesulfonate (Me4NOTs) solution at 25 degrees C. For purpose of comparison, the complexation of the polyamine-ATP systems were also considered in the same experimental conditions. 31P-NMR experiments showed for Ins(1,4,5)P3 and its analogues, the formation of complexes of a 1:1 stoichiometry. As expected, the most stable complexes are formed between the most charged partners. In addition, the basicity of the phosphate groups seems to govern the stability of the complexes. If both ATP and Ins(1,4,5)P3 are present at the same concentration, the latter interacts preferably with the polyamines. Ins(1,4,5)P3-spermine complex formation provides a possible simple explanation for the inhibition by spermine of Ins(1,4,5)P3-induced Ca2+ release. Spermine will undoubtedly compete with metallic cations such as Ca2+ in the intracellular medium and consequently, may play a regulatory role in the signal transduction mediated by Ins(1,4,5)P3.
Mernissi-Arifi
K
K
Laboratoire de Pharmacochimie Moléculaire, UPR 421 du CNRS, Faculté de Pharmacie, Illkirch, France.
Imbs
I
I
Schlewer
G
G
Spiess
B
B
D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D011522:Protons; D015398:Signal Transduction; D013095:Spermidine / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism*
D008024:Ligands; D011522:Protons; D013096:Spermine; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D013095:Spermidine