Relationship between inositol 1,4,5-trisphosphate mass level and [14C]aminopyrine uptake in gastrin-stimulated parietal cells.

The relationship between gastrin-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) content and [14C]aminopyrine ([14C]AP) uptake (an index of in vitro acid secretion) was investigated in a population of highly enriched rabbit parietal cells (90 +/- 5%). Gastrin induced a rapid rise in Ins(1,4,5)P3 content which was maximal within 15 s of stimulation (2- to 2.5-fold basal level) followed by a rapid decrease within 30 s; a high Ins(1,4,5)P3 level could also be observed after a longer time of hormone stimulation (180 s). Gastrin dose-dependently induced Ins(1,4,5)P3 accumulation and [14C]AP uptake; both dose-response curves were similar (EC50 approximately 0.1 nM). Furthermore, L-365,260 (3-(acylamino)benzodiazepine), a selective gastrin/CCK-B receptor antagonist, dose-dependently inhibited Ins(1,4,5)P3 production and [14C]AP accumulation induced by 10 nM gastrin with a similar potency (IC50 approximately 1-2 nM). These results led us to conclude that Ins(1,4,5)P3 is involved in gastrin-stimulated acid secretory activity of gastric parietal cells.