Sucrose octasulfate stimulates gastric somatostatin release.
To explore the mechanisms of the effects of sucralfate on the stomach, we investigated the action of sucrose octasulfate (SOS), a constituent of sucralfate, on the function of canine gastric parietal cells and somatostatin cells and in the isolated perfused intact rat stomach. Somatostatin cells from the canine gastric fundus were isolated by EDTA-collagenase dispersion and counterflow elutriation, and somatostatin-like immunoreactivity (SLI) release in response to SOS was measured by radioimmunoassay. Similar methods were used to isolate gastric parietal cells, in which gastric acid secretion was measured by uptake of a radiolabeled weak base, [14C]aminopyrine. SLI release by the intact rat stomach was examined in an isolated vascularly perfused rat stomach model. SOS, either alone or co-administered with epinephrine or gastrin heptadecapeptide (G17), dose-dependently stimulated SLI release by isolated canine fundic D-cells. At the highest doses, SOS potentiated the effect of epinephrine but not G17. Similarly, SOS potentiated the stimulating effect of dibutyryl cyclic adenosine 3',5'-monophosphate (DBcAMP), but not 12-O-tetradecanoylphorbol 13-acetate (TPA). The effect of SOS on SLI release could be inhibited by octreotide, a somatostatin analogue. SOS did not alter acid secretion by cultured canine parietal cells either in the basal state or when coadministered with acid secretagogues. In isolated perfused rat stomach studies, SOS produced a significant (60% greater than basal) increase in SLI secretion. There was a similar effect when SOS was perfused against a background of isoproterenol. SOS stimulates SLI release from gastric somatostatin cells and from the isolated perfused stomach but has no direct effect on gastric parietal cells. These actions of SOS may mediate in part the apparent ability of sucralfate to enhance gastric mucosal defense.
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0362.
M R
MR
Lucey
J
J
Park
J
J
DelValle
L D
LD
Wang
T
T
Yamada
D000632:Aminopyrine / Q000493:pharmacokinetics; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D005748:Gastric Fundus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015282:Octreotide / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000737:chemistry / Q000378:metabolism*; D013395:Sucrose / Q000031:analogs & derivatives* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005755:Gastrins; D010455:Peptides; C029993:somatostatin-like peptides; D000632:Aminopyrine; D013004:Somatostatin; D013395:Sucrose; C013550:gastrin 17; D003994:Bucladesine; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; C053081:sucrose octasulfate; D015282:Octreotide; D004837:Epinephrine