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 possible ways to deplete ECL cells of histamine without affecting pancreastatin and to examine how histamine depletion affects pancreastatin secretion. Isolated rat stomach ECL cells (80-85% purity), prepared by counter-flow elutriation, were cultured for 48 h in the presence of alpha-fluoromethylhistidine (histidine decarboxylase inhibitor), bafilomycin A(1) (inhibitor of vacuolar-type proton-translocating ATPase) or reserpine (inhibitor of vesicular monoamine transporter). At this stage, the cells were challenged with 10 nM (EC(100)) gastrin-17 for 30 min. Histamine and pancreastatin were determined by radioimmunoassay. Maximally effective concentrations of alpha-fluoromethylhistidine, bafilomycin A(1) and reserpine were found to lower ECL-cell histamine (by 60%, 78% and 80%, respectively) without affecting pancreastatin. Basal histamine secretion was reduced in a dose-dependent manner by all three drugs. Gastrin-evoked histamine secretion was reduced greatly by the three agents, while pancreastatin secretion was unaffected. The results show that histamine can be depleted not only by inhibiting its formation (alpha-fluoromethylhistidine), but also (and more effectively) by inhibiting histamine vesicular uptake, directly (reserpine) or indirectly (bafilomycin A(1)). The results also indicate that although histamine is co-stored with pancreastatin, it is not required for either storage or secretion of pancreastatin.
Lindström
E
E
Institute of Physiological Sciences, Department of Pharmacology, University of Lund, Sölvegatan 10, S-223 62, Lund, Sweden.
Norlén
P
P
Håkanson
R
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002478:Cells, Cultured; D053379:Chromogranin A; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D018942:Macrolides; D010187:Pancreatic Hormones / Q000378:metabolism*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D053379:Chromogranin A; D018942:Macrolides; D010187:Pancreatic Hormones; C050836:pancreastatin; C054284:alpha-fluoromethylhistamine; D006632:Histamine; C040929:bafilomycin A1; D012110:Reserpine