AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 5 596-G602, Copyright © 1988 by American Physiological Society
Gastrin secretion by gastrinoma cells in long-term culture
L. Elouaer-Blanc, I. Sobhani, P. Ruszniewski, M. Duet, T. Lehy, M. Mignon, S. Bonfils and M. J. Lewin
Institut National de la Sante et de la Recherche Medicale U.10, Hopital Bichat, Paris, France.
Gastrinoma cells from surgical specimens of a primary pancreatic tumor and
an hepatic metastasis in two patients with a Zollinger-Ellison syndrome
were grown and subcultured for 7 mo. Cultured cells displayed a strong
reactivity to heptadecapeptide gastrin antibody and maintained an
ultrastructural appearance resembling that of the original tumor cells with
the presence of secretory granules of variable size and electron density.
Cultured cells also showed the ability to secrete immunoreactive gastrin,
and this secretion was further concentration-dependently stimulated by
secretin (10(-10)-10(-6) M), carbachol (10(-6) M), and bombesin
(10(-10)-10(-6) M). The latter peptide was the more potent stimulant with a
maximal effect at 10(-9) M (460 +/- 20% of basal release; P less than
0.05). This stimulation occurred in the absence of extracellular Ca2+ and
was potentiated by the addition of dibutyryl adenosine 3',5'-cyclic
monophosphate (DBcAMP; 10(-3) M) into the culture medium. The somatostatin
analogue, somatostatin-(201-995), did not alter basal gastrin release but
inhibited secretin, carbachol, and bombesin stimulation. Moreover, DBcAMP
(10(-3) M) and Ca2+ (1-3 mM) stimulated gastrin release; Ca2+ ionophore
A23187 (6 micrograms/ml) enhanced gastrin response to Ca2+ in the early
time intervals of incubation. Furthermore the phorbol ester derivative,
12-O-tetradecanoyl phorbol-13-acetate, dramatically stimulated gastrin
release (10 times the basal value). We conclude that gastrinoma cells can
be cultured over an extended period with maintenance of their capacity to
secrete gastrin in response to various hormones and mediators.(ABSTRACT
TRUNCATED AT 250 WORDS)
