Parallel secretion of pancreastatin and somatostatin from human pancreastatin producing cell line (QGP-1N).
In this investigation we studied pancreastatin (PST) secretion from a human PST producing cell line (QGP-1N) in response to various secretagogues. Immunocytochemical study revealed the immunoreactivity of PST and somatostatin (SMT) in the same cells of a monolayer culture. Ki-ras DNA point mutation on codon 12 was found. Carbachol stimulated secretion of PST and SMT and intracellular Ca2+ mobilization in the range of 10(-6)-10(-4) M. The secretion and Ca2+ mobilization were inhibited by atropine, a muscarinic receptor antagonist. Phorbol ester and calcium ionophore (A23187) stimulated secretion of PST and SMT. The removal of extracellular calcium suppressed both secretions throughout stimulation with 10(-5) M carbachol. Fluoride, a well-known activator of guanine nucleotide binding (G) protein, stimulated intracellular Ca2+ mobilization and secretion of PST and SMT in a dose-dependent manner in the range of 5-40 mM. Also, 10(-5) M carbachol and 20 mM fluoride stimulated inositol 1,4,5-triphosphate production. However, cholecystokinin and gastrin-releasing peptide did not stimulate Ca2+ mobilization or secretion of the two peptides. These results suggest that secretion of PST and SMT from QGP-1N cells is regulated mainly by acetylcholine in a parallel fashion through muscarinic receptors coupled to the activation of polyphosphoinositide breakdown by a G-protein and that increases in intracellular Ca2+ and protein kinase C play an important role in stimulus-secretion coupling.
Funakoshi
A
A
Department of Gastroenterology, Fukuoka University, Japan.
Tateishi
K
K
Kitayama
N
N
Jimi
A
A
Matsuoka
Y
Y
Kono
A
A
D007516:Adenoma, Islet Cell / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D053379:Chromogranin A; D011905:Genes, ras; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010187:Pancreatic Hormones / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D053379:Chromogranin A; D010187:Pancreatic Hormones; C050836:pancreastatin; D013004:Somatostatin; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D012844:Sincalide; D002118:Calcium