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 secretion. Its cellular target is unknown. The aim of this study was to determine whether galanin inhibits Ca2+ signaling and histamine release in enterochromaffin-like (ECL) cells. Methods: Isolated rat ECL cells were purified to 85% homogeneity by a combination of elutriation, density 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 radioimmunoassay. Results: Reverse-transciption polymerase chain reaction of the ECL cell RNA showed a galanin type I receptor subtype. Galanin inhibited gastrin, Bay K8644, and KC depolarization-induced calcium mobilization and entry as well as reduced basal calcium levels. Pretreatment with pertussis toxin decreased the effect of galanin. Galanin inhibited basal and gastrin-stimulated histamine release by approximately 60% with a median effective concentration of 1.10(-10) mol/L. The inhibitory actions of galanin on histamine release and Ca2+ influx could 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 activation of a G(i,0) protein-coupled receptor.