title: Histamine-stimulated inositol phospholipid metabolism in bovine adrenal medullary cells: a kinetic analysis.
abstract: Histamine stimulation of bovine adrenal medullary cells rapidly activated phospholipase C. [3H]Inositol 1,4,5-trisphosphate [[3H]Ins(1,4,5)P3] levels were transiently increased (200% of basal values between 1 and 5 s) before declining to a new steady-state level of approximately 140% of basal values. [3H]Inositol 1,4-bisphosphate [[3H]Ins(1,4)P2] content increased to a maximal and maintained level of 250% of basal values after 1 s, whereas levels of [3H]inositol 1,3,4-trisphosphate [[3H]Ins(1,3,4)P3], [3H]inositol 1,3-bisphosphate, and [3H]inositol 4-monophosphate ([3H]Ins4P) increased more slowly. The rapid responses were not reduced by the removal of extracellular Ca2+, but they were no longer sustained over time. The turnover rates of selected inositol phosphate isomers have been estimated in the intact cell. [3H]Ins(1,4,5)P3 was rapidly metabolized (t1/2 of 11 s), whereas the other isomers were metabolized more slowly, with t1/2 values of 113, 133, 104, and 66 s for [3H]Ins(1,3,4)P3, [3H]Ins(1,4)P2, an unresolved mixture of [3H]inositol 1- and 3-monophosphate ([3H]Ins1/3P), and [3H]Ins4P, respectively. The calculated turnover rate of [3H]Ins(1,4,5)P3 was sufficient to account for the turnover of the combination of both [3H]Ins(1,4)P2 and [3H]Ins(1,3,4)P3 but not that of [3H]Ins1/3P or [3H]Ins4P. These observations demonstrate that histamine stimulation of these cells results in a complex Ca(2+)-dependent and -independent response that may involve the hydrolysis of inositol phospholipids in addition to phosphatidylinositol 4,5-bisphosphate.
authors.affiliation: Neuroscience Group, Faculty of Medicine, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Bunn
authors.forename: H I
authors.initials: HI
authors.lastname: Saunders
authors.forename: P R
authors.initials: PR
authors.lastname: Dunkley
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006632:Histamine / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000096:biosynthesis; D007536:Isomerism; D007700:Kinetics; D009355:Neomycin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D006632:Histamine; D009355:Neomycin