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Am J Physiol Gastrointest Liver Physiol (April 23, 2004). doi:10.1152/ajpgi.00431.2003
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Submitted on October 2, 2003
Accepted on April 12, 2004

Regional Gastric Contractility Alterations in a Diabetic Gastroparesis Mouse Model - Effects of Cholinergic and Serotoninergic Stimulation

Arlene N. James1, James P. Ryan2, Michael D. Crowell3, and Henry P. Parkman4*

1 Department of Medicine, Temple University School of Medicine, Philadephia, PA, USA
2 Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA
3 Department of Medicine, Mayo Clinic Scottsdale, Scottsdale, AZ, USA
4 Department of Medicine, Temple University School of Medicine, Philadephia, PA, USA; Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA

* To whom correspondence should be addressed. E-mail: henry.parkman{at}temple.edu.

The C57 BL/Ks/J db/db mouse develops hyperglycemia and has delayed gastric emptying which is improved with tegaserod, a partial 5-HT4 agonist. AIMS: To determine regional gastric contractility alterations in C57 BL/Ks/J db/db mice and to determine the effects of serotonin and tegaserod. METHODS: Contractile effects of bethanechol, serotonin, and tegaserod in fundic, antral, and pyloric circular muscle were compared in C57 BL/Ks/J db/db mice and normal litter mates. Effects of tetrodotoxin, atropine, and 5-HT receptor antagonists were studied. RESULTS: Contractions in response to bethanechol were decreased in the fundus, similar in the antrum, but increased in the pylorus in diabetic mice compared to controls. Serotonin, and to a lesser extent tegaserod, caused contractions which were more pronounced in the fundus than the antrum and pylorus in both diabetic and normal mice. Serotonin-induced contractions were partially inhibited by atropine and the 5-HT4 antagonist GR113808 and the 5-HT2 antagonist cinanseron but not tetrodotoxin. CONCLUSIONS: Regional gastric contractility alterations are present in this diabetic gastroparesis mouse model. Fundic contractility was decreased, but pyloric contractility was increased in the pylorus, to cholinergic stimulation in diabetic mice. Serotonin's contractile effect is mediated in part through muscarinic, 5-HT2 and 5-HT4 receptors. This study suggests that fundic hypomotility and pyloric hypercontractility, rather than antral hypomotility, play important roles for the gastric dysmotility that occurs in diabetes.




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