Gastrin secretion from human antral G cells in culture.
Receptor-dependent and -independent regulation of gastrin secretion from cultured human antral G cells was investigated. Human antral mucosal cell preparations that were enriched for G cells were obtained by sequential incubations with collagenase and ethylenediaminetetraacetic acid, centrifugal elutriation, and short-term culture. After a 2-day incubation period, gastrin- and somatostatin-containing cells accounted for 15% and 5%, respectively, of the total adhered-cell population. Forskolin, A23187, and beta-phorbol 12 myristate 13-acetate stimulated basal gastrin secretion from cultured human G cells in a concentration-dependent fashion. These results indicate that gastrin release could be mediated by elevations in cytosolic cyclic adenosine monophosphate levels, calcium influx, or activation of protein kinase C. A direct stimulatory role for bombesin- and gastrin-releasing peptide was supported by experiments showing concentration-dependent enhancement of gastrin release by bombesin from 0.01 fmol/L to 10 nmol/L. The putative bombesin antagonist [Leu13-psi-CH2NH-Leu14] bombesin augmented basal gastrin levels by itself and produced weak inhibition of bombesin-induced gastrin secretion from human antral G cells. Somatostatin potently suppressed forskolin- and bombesin-mediated gastrin release but did not significantly alter basal gastrin levels. These results suggest that bombesin and somatostatin directly activate and inhibit G-cell function via specific and sensitive receptors. Furthermore, the adenylate cyclase and phosphatidyl inositide second messenger systems seem to be intracellular mediators of gastrin secretion from human antral G cells.
Campos
R V
RV
Department of Physiology, University of British Columbia, Vancouver, Canada.
Buchan
A M
AM
Meloche
R M
RM
Pederson
R A
RA
Kwok
Y N
YN
Coy
D H
DH
D001839:Bombesin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002838:Chromaffin System / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D011706:Pyloric Antrum / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005755:Gastrins; D011964:Receptors, Gastrointestinal Hormone; D005576:Colforsin; D000001:Calcimycin; D013004:Somatostatin; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin