Metabolism of inositol 1,4,5-trisphosphate in permeabilized rat aortic smooth-muscle cells. Dependence on calcium concentration.
The metabolism of [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3) was studied in permeabilized rat aortic smooth-muscle cells. Addition of [3H]Ins(1,4,5)P3 to the leaky cells led to formation of several labelled metabolites. Amounts of [3H]inositol bisphosphate and [3H]inositol 1,3,4,5-tetrakisphosphate ([3H]InsP4) reached a maximum within 2 min of incubation, whereas production of [3H]inositol monophosphate and [3H]inositol 1,3,4-trisphosphate ([3H]Ins(1,3,4)P3) was delayed. Formation of InsP4 and Ins(1,3,4)P3 was Ca2+-sensitive in the physiological intracellular range (0.06-5 microM), showing a maximum at 1 microM-Ca2+. A correlation between the formation of InsP4 and that of Ins(1,3,4)P3 was observed, suggesting that the former is the precursor of the latter. These results suggest that, in vascular smooth-muscle cells, Ins(1,4,5)P3 is metabolized via two distinct pathways: (1) a dephosphorylation pathway, leading to formation of inositol bis- and mono-phosphate; and (2) a Ca2+-sensitive phosphorylation/dephosphorylation pathway, involving formation of InsP4 and leading to formation of Ins(1,3,4)P3.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*
D007295:Inositol Phosphates; D013403:Sugar Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium