title: Time course of hypertrophic and ultrastructural responses of rat stomach enterochromaffin-like cells to sustained hypergastrinemia.
abstract: Previously, we have investigated the effects of short-term (minutes to hours) and long-term (weeks to months) stimulation with gastrin on the histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa of rat stomach. The present study examines the response of the ECL cells of freely fed rats to sustained hypergastrinemia over a time span of a few hours to four weeks. Sustained hypergastrinemia was induced by the continuous subcutaneous infusion of human Leu15-gastrin-17. The histidine decarboxylase (HDC) activity and histamine concentration in the oxyntic mucosa were monitored throughout the study. ECL cell profiles in electron micrographs were analysed planimetrically. The HDC activity displayed a 4-fold increase within the first two days. Subsequently, it remained at a plateau. The histamine concentration increased 2- to 3-fold in response to gastrin. The rise in histamine was slower than the rise in HDC activity. At no time point was there a reduced concentration of histamine. The ECL cells increased in size after 4 days of hypergastrinemia, reaching a maximum cell profile area after 2 weeks and remaining enlarged for the duration of the study. The secretory vesicles were reduced in number after 1 day, returning gradually to the pre-stimulation value thereafter; their volume density remained reduced during the 6-day observation period. Vacuoles started to appear after 1 day of hypergastrinemia and their number and volume density increased, reaching a maximum after 4 days. The number and volume density of the microvesicles increased and plateaued after 2 days of hypergastrinemia. The number of granules per cell profile was unaffected but their volume density was greatly reduced after 4 days of hypergastrinemia (reflecting the ECL cell hypertrophy). The present findings establish the time course of activation of the ECL cells in response to sustained hypergastrinemia over a time span of a few hours to four weeks; a new "steady state" situation at a high level of activity has been established after about a week.
authors.affiliation: Department of Pharmacology, University of Lund, Sölvegatan 10, S-223 62 LUND, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: C M
authors.initials: CM
authors.lastname: Zhao
authors.forename: A G
authors.initials: AG
authors.lastname: Nylander
authors.forename: R
authors.initials: R
authors.lastname: Håkanson
mesh_terms: D000818:Animals; D004759:Enterochromaffin Cells / Q000201:enzymology / Q000648:ultrastructure*; D005753:Gastric Mucosa / Q000166:cytology* / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D006640:Histidine Decarboxylase / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy / Q000503:physiopathology; D008297:Male; D051381:Rats; D013997:Time Factors
chemical_list: D005755:Gastrins; D006640:Histidine Decarboxylase