Premium
Histamine‐Stimulated Inositol Phospholipid Metabolism in Bovine Adrenal Medullary Cells: A Kinetic Analysis
Author(s) -
Bunn Stephen J.,
Saunders Heather I.,
Dunkley Peter R.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65020626.x
Subject(s) - inositol , medicine , inositol phosphate , endocrinology , histamine , phospholipid , stimulation , phosphatidylinositol , inositol trisphosphate , chemistry , extracellular , metabolism , phospholipase , calcium , biology , biochemistry , enzyme , receptor , signal transduction , membrane
Histamine stimulation of bovine adrenal medullary cells rapidly activated phospholipase C. [ 3 H]Inositol 1,4,5‐trisphosphate [[ 3 H]Ins(1,4,5)P 3 ] levels were transiently increased (200% of basal values between 1 and 5 s) before declining to a new steady‐state level of ∼140% of basal values. [ 3 H]Inositol 1,4‐bisphosphate [[ 3 H]Ins(1,4)P 2 ] content increased to a maximal and maintained level of 250% of basal values after 1 s, whereas levels of [ 3 H]inositol 1,3,4‐trisphosphate [[ 3 H]‐Ins(1,3,4)P 3 ], [ 3 H]inositol 1,3‐bisphosphate, and [ 3 H]‐inositol 4‐monophosphate ([ 3 H]Ins4P) increased more slowly. The rapid responses were not reduced by the removal of extracellular Ca 2+ , but they were no longer sustained over time. The turnover rates of selected inositol phosphate isomers have been estimated in the intact cell. [ 3 H]Ins(1,4,5)P 3 was rapidly metabolized ( t 1/2 of 11 s), whereas the other isomers were metabolized more slowly, with t 1/2 values of 113, 133, 104, and 66 s for [ 3 H]Ins(1,3,4)P 3 , [ 3 H]Ins(1,4)P 2 , an unresolved mixture of [ 3 H]inositol 1‐ and 3‐monophosphate ([ 3 H]Ins1/3P), and [ 3 H]Ins4P, respectively. The calculated turnover rate of [ 3 H]Ins(1,4,5)P 3 was sufficient to account for the turnover of the combination of both [ 3 H]Ins(1,4)P 2 and [ 3 H]Ins(1,3,4)P 3 but not that of [ 3 H]Ins1/3P or [ 3 H]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.