GALANIN INHIBITION OF ENTEROCHROMAFFIN-LIKE CELL-FUNCTION

Background & Aims: Galanin, a 29-amino acid neuropeptide found in the gastric mucosa, inhibits basal and pentagastrin-stimulated acid secret ion. Its cellular target is unknown. The aim of this study was to dete rmine whether galanin inhibits Ca2+ signaling and histamine release in enterochromaffin-like (ECL) cells. Methods: Isolated rat ECL cells we re purified to 85% homogeneity by a combination of elutriation, densit y gradient centrifugation, and 48-hour culture. Intracellular calcium concentration ([Ca2+](i)) was determined using video imaging with Fura -2 in a 37 degrees C superfusion chamber. Histamine was measured by ra dioimmunoassay. Results: Reverse-transciption polymerase chain reactio n of the ECL cell RNA showed a galanin type I receptor subtype. Galani n inhibited gastrin, Bay K8644, and KC depolarization-induced calcium mobilization and entry as well as reduced basal calcium levels. Pretre atment with pertussis toxin decreased the effect of galanin. Galanin i nhibited basal and gastrin-stimulated histamine release by approximate ly 60% with a median effective concentration of 1.10(-10) mol/L. The i nhibitory actions of galanin on histamine release and Ca2+ influx coul d be reduced by a galanin antagonist, galantide. Conclusions: Galanin' s inhibition of acid secretion can be explained in part by inhibition of calcium signaling and histamine release from the ECL cells due to a ctivation of a G(i,0) protein-coupled receptor.