Production and secretion of chromogranin A and pancreastatin by the human pancreatic carcinoma cell line QGP-1N on stimulation with carbachol.
Chromogranin A (CGA) is thought to be a precursor of pancreastatin (PST). Carbachol (Cch) stimulated the secretion of CGA and PST from QGP-1N cells derived from a human pancreatic islet cell tumor. Atropine inhibited the secretion of both. Sodium fluoride, phorbol ester, and calcium ionophore also stimulated the secretion of both. Cch (10(-5) M) stimulated inositol 1,4,5-trisphosphate production in QGP-1N cells. Stimulation with Cch increased the total amount of PST in the cells and the medium 1.7-fold and decreased the amount of CGA in the cells and medium. QGP-1N cells were labelled with [35S]methionine, and then CGA and PST in the cells and medium were immunoprecipitated with specific antisera, and separated by electrophoresis in polyacrylamide gel. Stimulation with Cch resulted in an increase in the intensity of PST-immunoreactive bands and a decrease in those of CGA-immunoreactive bands. Cch did not increase the cellular level of CGA messenger RNA. These results suggested that (1) the secretion of CGA and PST from QGP-1N cells is regulated mainly through muscarinic receptors coupled with activation of polyphosphoinositide breakdown by a G protein, with intracellular calcium ion and protein kinase C playing a role in the stimulus-secretion coupling and that (2) Cch may induce the secretion of PST and CGA and processing from CGA to PST.
Kitayama
N
N
First Department of Biochemistry, School of Medicine, Fukuoka University, Japan.
Tateishi
K
K
Funakoshi
A
A
Kono
A
A
Matsuoka
Y
Y
D018273:Carcinoma, Islet Cell / Q000503:physiopathology*; D053379:Chromogranin A; D002864:Chromogranins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D003470:Culture Media; D006801:Humans; D010187:Pancreatic Hormones / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D003470:Culture Media; D010187:Pancreatic Hormones; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; C050836:pancreastatin