Bombesin-evoked gastrin release and calcium signaling in human antral G cells in culture.
Amplification of mRNA from a human antral cell culture preparation demonstrated the presence of two receptors of the bombesin and gastrin-releasing peptide family, GRPR-1 and BRS-3. Single cell microfluorometry demonstrated that most cells that exhibited bombesin-evoked changes in intracellular Ca2+ concentration were gastrin immunoreactive, indicating that antral G cells express the GRPR subtype. There were two components to the intracellular Ca2+ response: an initial nitrendipine-insensitive mobilization followed by a sustained phase that was inhibited by removal of extracellular Ca2+ and 20 mM caffeine and was partially inhibited by 10 microM nitrendipine. Preexposure of cells to thapsigargin and caffeine prevented the response to bombesin, indicating activation of inositol 1,4,5-trisphosphate (IP3)-sensitive stores. Gastrin release could be partially reversed by removal of extracellular Ca2+ and blockade of L-type voltage-dependent Ca2+ channels, indicating that a component of the secretory response to bombesin was dependent on Ca2+ influx. These data demonstrated that bombesin-stimulated gastrin release from human antral G cells resulted from activation of GRPRs and involved both release of intracellular Ca2+ and influx of extracellular Ca2+ through a combination of L-type voltage-gated and IP3-gated Ca2+ channels.
Squires
P E
PE
Department of Physiology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Meloche
R M
RM
Buchan
A M
AM
D000293:Adolescent; D000328:Adult; D001839:Bombesin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011706:Pyloric Antrum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018004:Receptors, Bombesin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005755:Gastrins; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3; D001839:Bombesin; D002118:Calcium