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Specific inositol phosphates inhibit basal and calmodulin‐stimulated Ca 2+ ‐ATPase activity in human erythrocyte membranes in vitro and inhibit binding of calmodulin to membranes
Author(s) -
Davis Faith B.,
Davis Paul J.,
Lawrence William D.,
Blas Susan D.
Publication year - 1991
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.5.14.1836436
Subject(s) - calmodulin , inositol , inositol phosphate , red blood cell , atpase , membrane , biochemistry , chemistry , inositol trisphosphate , calcium , in vitro , enzyme , receptor , organic chemistry
d ‐ Myo ‐inositol 1,4,5‐trisphosphate (Ins[1,4‐,5]P 3 ) inhibits rat heart sarcolemmal Ca 2+ ‐ATPase activity (T. H. Kuo, Biochem. Biophys. Res. Commun. 152: 1111, 1988). We have studied the effect and mechanism of action of Ins(1,4,5)P 3 and related inositol phosphates on human red cell membrane Ca 2+ ‐ATPase (EC 3.6.1.3) activity in vitro. At 10 –6 m , Ins(1,4,5)P 3 and d ‐ myo ‐inositol 4,5‐bisphosphate (Ins[4,5]P 2 ) inhibited human erythrocyte membrane Ca 2+ ‐ATPase activity in vitro by 42 and 31%, respectively. d ‐ Myo ‐inositol 1,3,4,5‐tetrakisphosphate, d ‐ myo ‐inositol 1,4‐bisphosphate, and d ‐ myo ‐inositol 1‐phosphate were not inhibitory. Enzyme inhibition by Ins(1,4,5)P 3 was blocked by heparin. Exogenous purified calmodulin also stimulated red cell membrane Ca 2+ ‐ATPase activity; this stimulation was inhibited by Ins(1,4,5)P 3 . Ins(4,5)P 2 and Ins(1,4,5)P 3 , but not Ins(1,4)P 2 , inhibited the binding of [ 125 I]calmodulin to red cell membranes. Thus, specific inositol phosphates reduce plasma membrane Ca 2+ ‐ATPase activity and enhancement of the latter in vitro by purified calmodulin. The mechanism of these effects may in part relate to inhibition by inositol phosphates of binding of calmodulin to erythrocyte membranes.—Davis, F. B.; Davis, P. J.; Lawrence, W. D.; Blas, S. D. Specific inositol phosphates inhibit basal and calmodulin‐stimulated Ca 2+ ‐ATPase activity in human erythrocyte membranes in vitro and inhibit binding of calmodulin to membranes. FASEB J. 5: 2992‐2995; 1991.