Gastrin-releasing peptide mobilizes calcium from intracellular stores in HIT-T15 cells.

The mechanism by which gastrin-releasing peptide (GRP) increases cytoplasmic calcium [Ca2+]ic was studied in insulin-producing HIT-T15-cells. At zero glucose, GRP (100 nM) rapidly increased [Ca2+]ic in the presence and absence of extracellular Ca2+. The effect was potentiated by glucose, impaired by the inhibitor of microsomal Ca(2+)-ATPase, thapsigargin, and abolished by the inhibitor of phospholipase C U73122. In contrast, the inhibitor of Ca2+ induced Ca2+ release, ryanodine, was without effect. Furthermore, the GRP-induced increase in [Ca2+]ic was potentiated by forskolin and impaired by activation of protein kinase C (PKC) by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Based on these results, we conclude: 1) that GRP mobilizes Ca2+ from a thapsigargin-sensitive intracellular Ca2+ pool through activation of phospholipase C, and 2) that the GRP-induced mobilization of Ca2+ is potentiated by cyclic AMP.