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The effects of tegaserod, a 5‐HT 4 receptor agonist, on gastric emptying in a murine model of diabetes mellitus
Author(s) -
Crowell M. D.,
Mathis C.,
Schettler V. A.,
Yunus T.,
Lacy B. E.
Publication year - 2005
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2005.00681.x
Subject(s) - gastric emptying , tegaserod , gastroparesis , agonist , medicine , endocrinology , stomach , gastroenterology , chemistry , receptor , constipation
The C57BLKS/J db/db transgenic mouse is a model of diabetes mellitus that has been shown to have delayed gastric emptying. We assessed gastric emptying rates in C57BLKS/J mice, and determined the effects of tegaserod, a new selective 5‐HT 4 receptor partial agonist, on gastric emptying. Methods: Gastric emptying rates of a 20% glucose test meal were determined in 12–20‐week‐old female db/db mice and control littermates. The effects of tegaserod (0.1–2.0 mg kg −1 , i.p.) on gastric transit were tested in a second group of db/db mice. Pretreatment with GR11308, a specific 5‐HT 4 antagonist, was used to confirm the mechanism of action of tegaserod on gastric emptying . Results: Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg −1 ) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod. Conclusions: Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5‐HT 4 receptors. These findings suggest that 5‐HT 4 receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis.