The effects of tegaserod, a 5-HT receptor agonist, on gastric emptying in a murine model of diabetes mellitus.
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.
Crowell
M D
MD
The Marvin M. Schuster Center for Digestive and Motility Disorders, Johns Hopkins University School of Medicine, Baltimore, MD, USA. crowell.michael@mayo.edu
Mathis
C
C
Schettler
V A
VA
Yunus
T
T
Lacy
B E
BE
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D044422:Receptors, Serotonin, 5-HT4 / Q000187:drug effects / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D001786:Blood Glucose; D007211:Indoles; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C105050:tegaserod; D005947:Glucose