Release of somatostatin immunoreactivity from human antral D cells in culture.
A primary culture of human antral somatostatin cells has been developed and used in release studies. The phorbol ester, phorbol 12 myristate 13-acetate, caused a concentration-dependent increase in immunoreactive somatostatin secretion with a 1-mumol/L concentration resulting in a 40-fold stimulation (basal 0.28% +/- 0.7% total cell content vs. 13.8% +/- 2.2% TCC, P less than 0.005). The calcium ionophore, A23187, resulted in a significant stimulation only at 1 mumol/L (basal 0.28% +/- 0.7% TCC vs. 2.2% +/- 0.5% total cell content, P less than 0.05). However, addition of the ionophore at 1 mumol/L with the phorbol ester resulted in a potentiation of the response at all concentrations tested. Removal of extracellular calcium by chelation with EGTA reduced the response to that seen with the phorbol ester alone. Forskolin at 0.1 mmol/L resulted in a five-fold increase (basal 0.6% +/- 0.2% total cell content vs. 2.8% +/- 0.9% total cell content, P less than 0.02) and was 1000-fold less potent than the phorbol ester. The peptides bombesin and gastrin at concentrations up to 1 mumol/L had no effect on basal secretion. Cholecystokinin-8 significantly stimulated somatostatin secretion with a maximal effect at 0.1 mumol/L resulting in an eightfold increase (basal 0.2% +/- 0.04% total cell content vs. 1.5% +/- 0.4% total cell content, P less than 0.02). These results indicate that human antral D cells are more responsive to agents acting through the c-kinase pathway (phorbol 12 myristate 13-acetate, A23187, and cholecystokinin) than adenylate cyclase (forskolin).
Buchan
A M
AM
Department of Physiology, University of British Columbia, Vancouver, Canada.
Curtis
S B
SB
Meloche
R M
RM
D000328:Adult; D001839:Bombesin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology; D006801:Humans; D008297:Male; D011706:Pyloric Antrum / Q000166:cytology; D011863:Radioimmunoassay; D012016:Reference Values; D012844:Sincalide / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005755:Gastrins; D005576:Colforsin; D000001:Calcimycin; D013004:Somatostatin; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin