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.
Department of Medicine, Lund University, Malmö, Sweden.
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S
Karlsson
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B
Ahrén
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D004963:Estrenes; D005768:Gastrointestinal Hormones; D010455:Peptides; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D012433:Ryanodine; D005576:Colforsin; D004533:Egtazic Acid; D019284:Thapsigargin; D019886:Gastrin-Releasing Peptide; D000242:Cyclic AMP; D011493:Protein Kinase C; D010738:Type C Phospholipases; D005947:Glucose; D002118:Calcium