INOSITOL PHOSPHATES MODULATE BINDING OF THYROID-HORMONE TO HUMAN RED-CELL MEMBRANES IN-VITRO

D-Myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] and D-myo-inositol 4,5-bisphosphate (10(-6) mol/L) displaced specifically bound L-[I-125] T-4 from human erythrocyte membranes in vitro by up to 80%. D-Myo-ino sitol 1,3,4,5-tetrakisphosphate, D-myo-inositol 1-monophosphate, and D -myo-inositol 1,4-bisphosphate were ineffective in decreasing thyroid hormone binding to membranes. The effect of Ins(1,4,5)P-3 on high affi nity binding reflected a change in K-d (5.8 x 10(-11) vs. 1.5 x 10(-11 ) mol/L) and binding capacity (15 vs. 2 fmol/mg membrane protein) in t he absence and presence of Ins(1,4,5)P-3, respectively. Ins(1,4,5)P-3 also displaced T-3 from red cell membranes. Thus, selected inositol ph osphates regulate the abundance of sites available for binding of thyr oid hormone by human red cell membranes. This stereospecific action of inositol phosphates is among several plasma membrane effects recently described for these members of the signal-transducing phosphoinositid e pathway.