Control of gastrin release in cultured gastrinoma-derived G cells.
Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000328:Adult; D002478:Cells, Cultured; D002838:Chromaffin System / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004759:Enterochromaffin Cells / Q000378:metabolism*; D005260:Female; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011863:Radioimmunoassay; D012633:Secretin / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015043:Zollinger-Ellison Syndrome / Q000378:metabolism*
D005755:Gastrins; D010703:Phorbol Esters; D012633:Secretin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C008876:phorbol-12,13-didecanoate; D013004:Somatostatin; D013755:Tetradecanoylphorbol Acetate