Gastrin and CCK-8 induce inositol 1,4,5-trisphosphate formation in rabbit gastric parietal cells.
The role of phosphoinositide turnover in the mediation of acid secretion was examined in an enriched preparation of isolated rabbit parietal cells (75%). Both gastrin and CCK-8 (octapeptide of cholecystokinin) stimulated [14C]aminopyrine (AP) uptake by cells (EC50 0.07 +/- 0.03 nM (gastrin) and 0.093 +/- 0.065 nM (CCK-8] and increased [3H]inositol phosphates cellular contents (EC50 0.142 +/- 0.016 nM (gastrin) and 0.116 +/- 0.027 nM (CCK-8] in a parallel fashion. In addition, the EC50 values for both phenomenon were quite similar to the Kd values obtained from binding experiments. HPLC analysis of the different [3H]inositol phosphates produced under gastrin or CCK-8 stimulation showed a 2-fold increase in [3H]Ins(1,4,5)P3 levels within 5 s with a concomitant increase in [3H]Ins(1,4)P2 content within 15 s. A low but significant rise in [3H]Ins(1,3,4,5)P4 and [3H]Ins(1,3,4)P3 cellular contents was also observed. No difference between gastrin- and CCK-8-induced inositol phosphates production could be shown. We can conclude that gastrin and CCK-8 display an identical profile of action, suggesting that they stimulate the acid secretory function of parietal cells through the same receptor site coupled to the Ins(1,4,5)P3 production.
Roche
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Laboratoire de Biochimie des Membranes, CNRS UPR-41, INSERM U-249, Faculté Pharmacie, Montpellier, France.
Magous
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R
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005755:Gastrins / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism*; D003012:Microbial Collagenase; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology*
D005755:Gastrins; D007295:Inositol Phosphates; D000632:Aminopyrine; D015544:Inositol 1,4,5-Trisphosphate; D003012:Microbial Collagenase; D012844:Sincalide