title: Ca2+ signaling through secretagogue and growth factor receptors on pancreatic AR42J cells.
abstract: Intracellular signaling by an increase in [Ca2+]i was observed in pancreatic AR42J cells in response to agonists whose receptors are G-protein coupled including cholecystokinin (CCK), bombesin, carbachol, substance P, pituitary adenylate cyclase activating peptide (PACAP), bradykinin, ATP, calcitonin gene related peptide (CGRP), and in response to growth factors EGF and FGF whose receptors are tyrosine kinases. The response to growth factors was smaller both in magnitude and in the percentage of cells responding but was independent of extracellular Ca2+. CCK and carbachol induced sizeable increases in inositol phosphates while growth factors did not. The responses to both carbachol and EGF, however, were blocked by the phospholipase C inhibitor U73122. The tyrosine kinase inhibitor, genestein, blocked the response to EGF but not that to CCK. These data are consistent with two types of signaling mechanisms in AR42J cells. Secretagogues act on receptors which couple through G proteins to induce a large amount of inositol phosphate production and subsequent intracellular Ca2+ mobilization. Growth factors act on receptors which signal through tyrosine kinase activity and in this cell type produced limited amounts of inositol phosphate and a smaller increase in intracellular Ca2+.
authors.affiliation: Department of Physiology, University of Michigan, Ann Arbor 48109, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Simeone
authors.forename: D I
authors.initials: DI
authors.lastname: Yule
authors.forename: C D
authors.initials: CD
authors.lastname: Logsdon
authors.forename: J A
authors.initials: JA
authors.lastname: Williams
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001839:Bombesin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000473:pathology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: C495403:Adcyap1 protein, rat; D004963:Estrenes; D007295:Inositol Phosphates; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011760:Pyrrolidinones; D018013:Receptors, Neuropeptide; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D013373:Substance P; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D002217:Carbachol; D002766:Cholecystokinin; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D015740:Calcitonin Gene-Related Peptide; D001839:Bombesin; D001920:Bradykinin; D002118:Calcium