title: Stimulation of hepatic inositol 1,4,5-trisphosphate kinase activity by Ca2+-dependent and -independent mechanisms.
abstract: A cytosolic fraction derived from rat hepatocytes was used to investigate the regulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] kinase, the enzyme which converts Ins(1,4,5)P3 to inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. The activity was doubled by raising the free Ca2+ concentration of the assay medium from 0.1 microM to 1.0 microM. A 5 min preincubation of the hepatocytes with 100 microM-dibutyryl cyclic AMP (db.cAMP) plus 100 nM-tetradecanoylphorbol acetate (TPA) resulted in a 40% increase in Ins(1,4,5)P3 kinase activity when subsequently assayed at 0.1 microM-Ca2+. This effect was smaller at [Ca2+] greater than 0.5 microM, and absent at 1.0 microM-Ca2+. Similar results were obtained after preincubation with 100 microM-db.cAMP plus 300 nM-vasopressin (20% increase at 0.1 microM-Ca2+; no effect at 1.0 microM-Ca2+). Preincubation with vasopressin, db.cAMP or TPA alone did not alter Ins(1,4,5)P3 kinase activity. It is proposed that these results, together with recent evidence implicating Ins(1,3,4,5)P4 in the control of Ca2+ influx, could be relevant to earlier findings that hepatic Ca2+ uptake is synergistically stimulated by cyclic AMP analogues and vasopressin.
authors.affiliation: Department of Biochemistry, Faculty of Science, Australian National University, Canberra, ACT.
authors.forename: T J
authors.initials: TJ
authors.lastname: Biden
authors.forename: J G
authors.initials: JG
authors.lastname: Altin
authors.forename: A
authors.initials: A
authors.lastname: Karjalainen
authors.forename: F L
authors.initials: FL
authors.lastname: Bygrave
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D010770:Phosphotransferases / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor); D051381:Rats; D013755:Tetradecanoylphorbol Acetate; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D014667:Vasopressins; D003994:Bucladesine; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium