Evidence for receptor-specific regulation of the metabolism of the second messenger, inositol trisphosphate, in human endothelial cells.
Primary cultures (1-2 weeks-old, no passage) of endothelial cells from the human umbilical vein were pre-labelled with [3H]inositol, stimulated for varying times (15 seconds to 5 minutes) in the presence of LiCl with either thrombin or histamine, and the extracted radiolabelled isomers of inositol phosphates were analysed by anion-exchange chromatography. The doses of each receptor-agonist were chosen to stimulate a large accumulation of inositol phosphates at approximately the same rate. At all times of stimulation the relative accumulation of inositol trisphosphate isomers and inositol tetrakisphosphate was different upon stimulation with these agonists, particularly at earlier times. These results argue for the receptor-specific regulation of the inositol trisphosphate 3-kinase. The significance of this observation is discussed with respect not only to the current ideas on the control of calcium homoeostasis by inositol phosphates, but also in consideration of their role as second messengers controlling different end-points of vascular function.
Department of Development and Signalling, Babraham Institute, Cambridge, UK.
K A
KA
Wreggett
R F
RF
Irvine
D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D002852:Chromatography, Ion Exchange; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism*; D007536:Isomerism; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008954:Models, Biological; D015290:Second Messenger Systems; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D014471:Umbilical Veins
D002712:Chlorides; D007295:Inositol Phosphates; D007294:Inositol; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D008094:Lithium; D013917:Thrombin; D018021:Lithium Chloride