Galanin inhibition of enterochromaffin-like cell function.
OBJECTIVE
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 degreesC 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 K+ 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 Gi,o protein-coupled receptor.
Department of Physiology and Medicine, UCLA, and Wadsworth VA Medical Center, Los Angeles, California, USA.
N
N
Zeng
T
T
Kang
Y
Y
Wen
H
H
Wong
J
J
Walsh
G
G
Sachs
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D004594:Electrophysiology; D019004:Galanin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D037342:Pertussis Toxin; D051381:Rats; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D010566:Virulence Factors, Bordetella; D006632:Histamine; D019004:Galanin; D037342:Pertussis Toxin; D002118:Calcium