INOSITOL 1,2,3-TRISPHOSPHATE AND INOSITOL 1,2-BISPHOSPHATE AND OR 2,3-BISPHOSPHATE ARE NORMAL CONSTITUENTS OF MAMMALIAN-CELLS/

1. An inositol trisphosphate (InsP(3)) distinct from Ins(1,4,5)P-3 and Ins(1,3,3)P-3, which we previously observed in myeloid and lymphoid c ells [French, Bunce, Stephens, Lord, McConnell, Brown, Creba and Miche ll(1991) Proc R, Sec. London B 245, 193-201; Bunce, French, Alien, Mou ntford, Moore, Greaves, Michell and Brown (1993) Biochem. J. 289, 667- 673], is present in WRK1 rat mammary tumour cells and pancreatic endoc rine beta-cells. 2. It has been identified as Ins(1,2,3)P-3 by a combi nation of oxidation to ribitol, a structurally diagnostic polyol, and ammoniacal hydrolysis to identified inositol monophosphates. 3. Ins(1, 2,3)P-3 concentration in HL60 cells changed little during stimulation by ATP or fMetLeuPhe or during neutrophilic or monocytic differentiati on, and Ins(1,2,3)P-3 was unresponsive to vasopressin in WRK1 cells. 4 . Ins(1,2,3)P-3 was usually more abundant than Ins(1,4,5)P-3, often be ing present at concentrations between similar to 1 mu M and similar to 10 mu M. 5. HL60, WRK-1 and lymphoid cells also contain Ins(1,2)P-2 o r Ins(2,3)P-2, or a mixture of these two enantiomers, as a major InsP( 3) species. 6. Ins(1,2,3)P-3 and Ins(1,2)P-2/Ins(2,3)P-2 are readily d etected in cells labelled for long periods, but not in acutely labeled cells. This behaviour resembles that of InsP(6), the most abundant ce llular inositol polyphosphate that includes the 1,2,3-trisphosphate mo tif, which also achieves isotopic equilibrium with inositol only slowl y. 7. Ins(1,2,3)P-3 is the major InsP(3) that accumulates during metab olism of InsP(6) by WRK-1 cell homogenates. 8. Possible metabolic rela tionships between Ins(1,2,3)P-3, Ins(1,2)P-2/Ins(2,3)P-2 and other ino sitol polyphosphates in cells, and a possible role for Ins(1,2,3)P-3 i n cellular iron handling, are considered.