Gastrin-evoked secretion of pancreastatin and histamine from ECL cells and of acid from parietal cells in isolated, vascularly perfused rat stomach. Effects of isobutyl methylxanthin and alpha-fluoromethylhistidine

The ECL cells in the rat stomach release pancreastatin and histamine in response to gastrin stimulation. The present study compares the release of pancreastatin and histamine from the ECL cells and the secretion of acid from the parietal cells in response to gastrin, and examines how a markedly reduced histamine content in the ECL cells will affect the gastrin-evoked release of pancreastatin and the secretion of gastric acid. Totally isolated, vascularly perfused stomachs were prepared from fasted rats. Some of the rats had been pre-treated for 24 h with (alpha-fluoromethylhistidine (alpha-FMH), resulting in 80% depletion of oxyntic mucosal histamine (mainly ECL-cell histamine). The stomachs were perfused with rat gastrin-17, alpha-FMH, isobutyl methylxanthine (IBMX), or vehicle in various combinations for 8 h. The venous outflow was collected (30-min samples) for determination of histamine and pancreastatin-like immunoreactivity (LI) and the gastric luminal outflow was collected for determination of H+. Gastrin raised the outflow of pancreastatin-LI, and histamine but did not raise the acid output unless IBMX was added. The outflow of pancreastatin-LI and histamine was greater after gastrin + IBMX (at least during the first 4-h period) than after gastrin alone. alpha-FMH reduced gastrin-evoked histamine outflow but did not affect gastrin-evoked pancreastatin-LI outflow. Also the acid output in response to gastrin + IBMX was much reduced by alpha-FMH. In conclusion, increased levels of intracellular cAMP enhanced the gastrin-evoked release of pancreastatin-LI and histamine from the ECL cells and made it possible for histamine, released from the ECL cells, to cause acid secretion from the parietal cells. ECL-cell histamine depletion reduced the gastrin-evoked acid secretion; it did not affect the gastrin-evoked release of pancreastatin-LI.