GASTRIN-EVOKED SECRETION OF PANCREASTATIN AND HISTAMINE FROM ECL CELLS AND OF ACID FROM PARIETAL-CELLS IN ISOLATED, VASCULARLY PERFUSED RATSTOMACH - EFFECTS OF ISOBUTYL METHYLXANTHIN AND ALPHA-FLUOROMETHYLHISTIDINE

The ECL cells in the rat stomach release pancreastatin and histamine i n response to gastrin stimulation. The present study compares the rele ase of pancreastatin and histamine from the ECL cells and the secretio n 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 gast ric 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 outflo w was collected (30-min samples) for determination of histamine and pa ncreastatin-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 unle ss IBMX was added. The outflow of pancreastatin-LI and histamine was g reater after gastrin + IBMX (at least during the first 4-h period) tha n after gastrin alone. alpha-FMH reduced gastrin-evoked histamine outf low but did not affect gastrin-evoked pancreastatin-LI outflow. Also t he acid output in response to gastrin + IBMX was much reduced by alpha -FMH. In conclusion, increased levels of intracellular cAMP enhanced t he gastrin-evoked release of pancreastatin-LI and histamine from the E CL cells and made it possible for histamine, released from the ECL cel ls, to cause acid secretion from the parietal cells. ECL-cell histamin e depletion reduced the gastrin-evoked acid secretion; it did not affe ct the gastrin-evoked release of pancreastatin-LI.