Hyperplastic G cell responsiveness in vitro

Abstract

To evaluate the responsiveness of isolated, hyperplastic antral gastrin-producing G cells to a variety of secretagogues, hyperplastic hypergastrinemia was produced in Sprague-Dawley rats by fundusectomy. Mean serum immunoreactive gastrin (IRG) concentration was elevated fivefold above controls 4 days after operation and rose steadily to an eightfold increase at 66 days. Mean antral G cell density remained at control levels for as long as 7 days, increased twofold at 14 days, then remained between twofold and threefold greater than controls for as long as 66 days after operation. Antral mucosa IRG content increased from 141 +/- 38 (control) to 262 +/- 58 ng IRG/gm mucosa (4 to 6 weeks after fundusectomy). Crude fractions of dispersed antral mucosa cells enriched in G cells from fundusectomized rats contained 6.5% +/- 1.4% G cells with 0.19 +/- 0.6 pg IRG/G cell. Corresponding preparations from nonoperated rats contained 5.1% +/- 0.5% G cells with 0.07 +/- 0.02 pg IRG/G cell. Viability averaged greater than 95% for all preparations. Gastrin secretion was monitored in cell preparations further enriched in G cells (9% to 10%) by Percoll density gradient centrifugation either in the absence (basal) or presence of bombesin (1 mumol, 1 nmol/L), carbachol (1 mmol/L), leucine (10 mmol/L), and ethylamine (10 mmol/L). The basal secretory rate of hyperplastic G cell populations averaged 250% greater than normal G cell basal rates. Hyperplastic G cell preparations had an increased IRG secretory rate in the presence of bombesin (1 mumol/L, 750%; 1 nmol/L, 191%), leucine (120%), ethylamine (236%), and carbachol (183%). These conditions failed to increase the IRG secretory rate above basal in preparations from normal antra. Viable, dispersed, hyperplastic G cells have increased IRG content and basal IRG secretory rate and are functionally responsive to a variety of secretagogues.