Colonic smooth muscle cells possess a different subtype of
somatostatin receptor than gastric smooth muscle cells.
Corleto, V. D., C. Severi, D. H. Coy, G. Delle Fave, and R. T. Jensen.
Digestive Diseases Branch, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health,
Bethesda, MD 20892, Peptide Research, Department of Medicine, Tulane
University School of Medicine, New Orleans, LA 70112, Digestive
Disease Unit, II Medical Clinic, University "LaSapienza",
00161, Rome, Italy
APStracts 3:0206G, 1996.
Previous studies demonstrate that somatostatin (SS) alters colonic
motility and colonic smooth muscle contractility both in vivo and in
vitro. To investigate whether SS has a direct or an indirect effect
on colonic smooth muscle cells we prepared isolated smooth muscle
cells from the descending guinea pig colon using collagenase
digestion. To compare SS's cellular basis of action on colonic cells
to a well-studied system we compared the effects of SS to those on
isolated gastric smooth muscle cells. SS-14 and SS-28 alone with
protease inhibitors [phosphoramidon (1 [mu]M) and amastatin (10
[mu]M)], caused contraction of colonic but not gastric smooth muscle
cells. With protease inhibitors present in gastric smooth muscle
cells SS-14 and SS-28 had no effect on carbachol-induced contraction,
whereas in colonic cells each caused a dose-related inhibition (SS-14
EC50 10 nM, SS-28 EC50 2.5 nM). In colonic muscle cells SS-28 caused
>85% inhibition of contraction by CCK-8, bombesin, the phorbol
ester, TPA, and the calcium ionophore, ionomycin, whereas it had no
effect on contraction by these agents in gastric muscle cells.
Without protease inhibitors, SS-14 and SS-28 had no effects on
contractants in colonic smooth muscle cells. In gastric muscle cells,
SS-14 and SS-28 inhibited VIP-stimulated relaxation with protease
inhibitors present; however, without protease inhibitors present, SS
-14 had no effect. Three synthetic SS analogues, octreotide, DC-23-99,
and NC-8-12 had different relative affinities for causing effects in
gastric and colonic smooth muscle cells. For colonic muscle cells,
the relative potencies for inhibiting carbachol-induced contraction
were DC-23-99>>octreotide>NC-8-12, and for
gastric cells for inhibiting VIP-induced relaxation were NC-8-12
nearly equal to DC-23-99 >octreotide. Pertussis toxin
inhibited the action of SS-28 in gastric and colonic smooth muscle
cells by 50-75%. When isolated smooth muscle cells were prepared
separately from the longitudinal and circular layers of the colon SS
-28 alone had a small but significant contractile effect on cells from
the circular layer. SS-28 inhibited carbachol-induced contraction in
cells from both layers. These results demonstrate the action of SS
differs in colonic and gastric smooth muscle cells. SS inhibits
contractants in colonic muscle cells and relaxants in gastric muscle
cells. SS has a weak contractant effect alone in colonic but not in
gastric muscle cells. In colonic muscle cells, the contractant effect
of SS alone is due to an effect in circular muscle cells, and the
inhibitory effect to its effect on both longitudinal and circular
layers. Furthermore, a different SS receptor subtype mediates the
actions of SS in colonic smooth muscle cells and in gastric smooth
muscle cells. Colonic cells possess an sst5-like subtype and gastric
cells likely possess an sst3 subtype. In both cell types the actions
of SS are mediated by pertussis-toxin sensitive and insensitive G
proteins.
Received 11 July 1995; accepted in final form 11 September 1996.
APS Manuscript Number G288-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996