Cysteamine can induce duodenal ulceration in rats without depletion of immunoreactive somatostatin.
Single subcutaneous administration of cysteamine (2-aminoethanethiol, CSH) produces duodenal ulceration in rats within 24 h. Depletion of circulating and tissue somatostatin (SOM), hypergastrinemia and gastric acid hypersecretion have all been postulated as the pathophysiological response to CSH leading to ulceration. The purpose of this study was to analyze the synthesis, storage and secretion of gastrin and SOM as well as structural changes in SOM peptide after CSH treatment. Injection of 300 mg/kg (s.c.) of CSH caused macroscopic duodenal ulcers in seven out of eight rats at 24 h. Hypergastrinemia was seen within 30 min (from 23 +/- 4 to 74 +/- 20 pmol/l), and persisted for 4 h. Antral gastrin content was elevated at 30 min (2539 +/- 114 pmol/g) when compared to saline controls (1589 +/- 101 pmol/g). Plasma SOM did not change over the 24 h but antral SOM increased at 30 min (from 120 +/- 3 to 230 +/- 23 pmol/g) and remained elevated at 2 h (374 +/- 48 pmol/g) and 4 h (357 +/- 37 pmol/g). Fundic and duodenal SOM followed a similar pattern. Antral SOM mRNA was also elevated over the first 4 h (3-fold increase, P less than 0.05). HPLC analysis of antral tissue extracts revealed the presence of additional molecular forms of SOM which, however, differed from the major products of in vitro reduction with either CSH or dithiothreitol. Thus, the in vivo effect of CSH on SOM cannot be solely explained by a reductive opening of the disulphide bond. These results suggest that duodenal ulceration in rats treated with CSH is not related in a simple fashion to depletion of immunoreactive SOM. Early induction of hypergastrinemia may be important in the onset of ulceration. The value of CSH as a SOM depleting tool in gastrointestinal tissue must remain in doubt.
University of Melbourne, Department of Surgery, Austin Hospital, Victoria, Australia.
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Kapuscinski
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Shulkes
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Green
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Read
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MacLellan
D000818:Animals; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D003543:Cysteamine / Q000633:toxicity*; D004247:DNA; D004381:Duodenal Ulcer / Q000139:chemically induced* / Q000378:metabolism; D005260:Female; D005755:Gastrins / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000276:immunology / Q000378:metabolism*
D005755:Gastrins; D012333:RNA, Messenger; D013004:Somatostatin; D003543:Cysteamine; D004247:DNA