Biphasic kinetics of inositol 1,4,5‐trisphosphate accumulation, in gastrin‐stimulated parietal cells Effects of pertussis toxin and extracellular calcium

FEBS Letters

Bali, Jean-Pierre¹  Gusdinar, Tutus¹  Magous, Richard¹  Roche, Serge¹ 

[1] Laboratoire de Biochimie des Membranes, CNRS UPR-8402-INSERM U-249, Faculté de Pharmacie, France

关键词: Gastrin;    Inositol 1;    4;    5-trisphosphate content;    Gastric parietal cell;    Pertussis toxin;    Extracellular Ca2+;    Ins(1;    4;    5)P3;    inositol (1;    4;    5)trisphosphate;    PTx;    pertussis toxin;    PL-C;    phospholipase C;    PtdInsP2;    phosphatidylinositol bisphosphate;   

DOI  :  10.1016/0014-5793(91)80465-F

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effect of Pertussis toxin (PTx) and extracellular Ca²⁺ were investigated on gastrin-induced Ins(1,4,5)P₃ mass level in isolated gastric parietal cells. Basal Ins(1,4,5)P₃ content was 5.48±0.49 pmol/500 000 cells. Gastrin (10 nM) induced a rapid increase in Ins(1,4,5)P₃ content which was maximal after 15 s and corresponded to 2–2.5-fold basal level; this Ins(1,4,5)P₃ 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)P₃ 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 Ca²⁺ did not affect the rapid rise, but drastically reduced the sustained increase in Ins(1,4,5)P₃ content (60–100% inhibition); this inhibition was not evident after 10 min of hormone stimulation. Furthermore, diltiazem, a Ca²⁺ channel blocker, led to a similar inhibition of the sustained increase. We concluded that: (i) gastrin induced rapid increase in Ins(1,4,5)P₃ content via a mechanism insensitive to PTx and to extracellular Ca²⁺, and (ii) gastrin induced a sustained increase in Ins(1,4,5)P₃ level via a mechanism sensitive to PTx and to extracellular Ca²⁺. Even though the rapid rise in Ins(1,4,5)P₃ content may be involved in the intracellular Ca²⁺ mobilization occurring after the first seconds of hormone stimulation, the physiological role of the sustained Ins(1,4,5)P₃ increased level remains to be elucidated.

【 授权许可】

Unknown