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Biphasic kinetics of inositol 1,4,5‐trisphosphate accumulation, in gastrin‐stimulated parietal cells Effects of pertussis toxin and extracellular calcium
Author(s) -
Roche Serge,
Gusdinar Tutus,
Bali Jean-Pierre,
Magous Richard
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80465-f
Subject(s) - pertussis toxin , extracellular , calcium , gastrin , inositol , chemistry , inositol trisphosphate , kinetics , microbiology and biotechnology , biophysics , receptor , endocrinology , biochemistry , biology , g protein , secretion , physics , organic chemistry , quantum mechanics
The effect of Pertussis toxin (PTx) and extracellular Ca 2+ were investigated on gastrin‐induced Ins(1,4,5)P 3 mass level in isolated gastric parietal cells. Basal Ins(1,4,5)P 3 content was 5.48±0.49 pmol/500 000 cells. Gastrin (10 nM) induced a rapid increase in Ins(1,4,5)P 3 content which was maximal after 15 s and corresponded to 2–2.5‐fold basal level; this Ins(1,4,5)P 3 content then decreased within 30 s. After a longer time of gastrin exposure (> 1 min), a sustained and unexpected increased in Ins(1,4,5)P 3 accumulation was observed which was maximal at 7.5 min (corresponding to 2.3–2.8‐fold basal value) and slightly decreased thereafter. PTx treatment of cells (200 ng/ml) for 3 h or removal extracellular Ca 2+ did not affect the rapid rise, but drastically reduced the sustained increase in Ins(1,4,5)P 3 content (60–100% inhibition); this inhibition was not evident after 10 min of hormone stimulation. Furthermore, diltiazem, a Ca 2+ channel blocker, led to a similar inhibition of the sustained increase. We concluded that: (i) gastrin induced rapid increase in Ins(1,4,5)P 3 content via a mechanism insensitive to PTx and to extracellular Ca 2+ , and (ii) gastrin induced a sustained increase in Ins(1,4,5)P 3 level via a mechanism sensitive to PTx and to extracellular Ca 2+ . Even though the rapid rise in Ins(1,4,5)P 3 content may be involved in the intracellular Ca 2+ mobilization occurring after the first seconds of hormone stimulation, the physiological role of the sustained Ins(1,4,5)P 3 increased level remains to be elucidated.