Crowell M D, Mathis C, Schettler V A, Yunus T, Lacy B E
The Marvin M. Schuster Center for Digestive and Motility Disorders, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Neurogastroenterol Motil. 2005 Oct;17(5):738-43. doi: 10.1111/j.1365-2982.2005.00681.x.
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.
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.
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.
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.
C57BLKS/J db/db转基因小鼠是一种糖尿病模型，已被证明存在胃排空延迟的情况。我们评估了C57BLKS/J小鼠的胃排空率，并确定了新型选择性5-HT(4)受体部分激动剂替加色罗对胃排空的影响。
测定12 - 20周龄雌性db/db小鼠和对照同窝小鼠对20%葡萄糖测试餐的胃排空率。在另一组db/db小鼠中测试替加色罗（0.1 - 2.0 mg kg(-1)，腹腔注射）对胃转运的影响。使用特异性5-HT(4)拮抗剂GR11308进行预处理，以确认替加色罗对胃排空的作用机制。
db/db小鼠的葡萄糖胃排空明显慢于对照同窝小鼠。替加色罗（0.1 mg kg(-1)）显著加快了db/db小鼠的葡萄糖胃排空率，使30分钟时胃中残留食物的比例降低了80%。GR11308阻断了替加色罗的促胃动力作用。
db/db小鼠存在胃排空受损的情况。低剂量替加色罗通过激活5-HT(4)受体改善了该胃轻瘫模型的胃排空率。这些发现表明5-HT(4)受体激动剂可能对改善胃轻瘫中的胃排空延迟有用。
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