Histamine depletion does not affect pancreastatin secretion from isolated rat stomach ECL cells

ECL cells co-secrete histamine and pancreastatin, a chromogranin A-derived peptide, in response to gastrin. The aim of the study was to explore possib le ways to deplete ECL cells of histamine without affecting pancreastatin a nd to examine how histamine depletion affects pancreastatin secretion. Isol ated rat stomach ECL cells (80-85% purity), prepared by counter-flow elutri ation, were cultured for 48 h in the presence of alpha-fluoromethylhistidin e (histidine decarboxylase inhibitor), bafilomycin A(1) (inhibitor of vacuo lar-type proton-translocating ATPase or reserpine (inhibitor of vesicular m onoamine transporter). At this stage, the cells were challenged with 10 nM (EC100) gastrin-17 for 30 min. Histamine and pancreastatin were determined by radioimmunoassay. Maximally effective concentrations of alpha-fluorometh ylhistidine, bafilomycin A(1) and reserpine were found to lower ECL-cell hi stamine (by 60%, 78% and 80%, respectively) without affecting pancreastatin . Basal histamine secretion was reduced in a dose-dependent manner by all t hree drugs. Gastrin-evoked histamine secretion was reduced greatly by the t hree agents, while pancreastatin secretion was unaffected. The results show that histamine can be depleted not only by inhibiting its formation (a-flu oromethylhistidine), but also land more effectively) by inhibiting histamin e vesicular uptake, directly (reserpine) or indirectly (bafilomycin A,). Th e results also indicate that although histamine is co-stored with pancreast atin, it is not required for either storage or secretion of pancreastatin. (C) 2000 Elsevier Science B.V. All rights reserved.