Linkage of [ca2+]i in single isolated d-cells to somatostatin
secretion induced by cholecystokinin.
Delvalle, J., J. Wakasugi, H. Takeda, and T. Yamada.
Departments of Internal Medicine and Physiology, The University of
Michigan Medical Center, Ann Arbor, Michigan 48109
APStracts 2:0243G, 1995.
The Ca2+/inositol phospholipid signaling cascade has been implicated
in the mechanism by which cholecystokinin (CCK) stimulates gastric
somatostatin release, but a direct linkage between intracellular
events in gastric D-cells and somatostatin secretion has not been
established. To address this problem we developed a method for
correlating somatostatin release with the measurement of [Ca2+]i in
isolated D-cells. Resting [Ca2+]i in single D-cells was 100 +/- 5.7
nM (mean +/- SE, n = 41) and CCK induced a rise in [Ca2+]i in a dose
dependent fashion, producing a maximal stimulatory effect (243 +/-
15% of control, n = 12) at a peptide concentration of 2 x 10-8M. The
CCK mediated increase in [Ca2+]i was biphasic, with a rapid, initial
transient elevation, followed by a sustained plateau. The rise in
[Ca2+]i was accompanied by a concomitant increase in release of
somatostatin like immunoreactivity (SLI). Removal of extracellular
Ca2+ had no effect on the initial transient elevation in [Ca2+]i
induced by CCK but abolished both the sustained plateau in [Ca2+]i
and the release of SLI. The selective CCK antagonist L-364,718 (10
-7M) inhibited the effects of CCK on both [Ca2+]i and SLI release. The
nonspecific Ca2+ channel blocker NiCl2 (10-3M) and the L-type calcium
channel blocker, nifedipine, inhibited the sustained rise in [Ca2+]i
and the release of SLI, but left unaltered the initial transient
increase in [Ca2+]i. These results indicate that CCK stimulated
release of SLI from D-cells in the gastric fundus is linked to influx
of extracellular Ca2+ via L-type Ca2+ channels.
Received 25 September 1995; accepted in final form 7 November
1995.
APS Manuscript Number G419-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95