Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2019.181
The Altered Signaling on EFS-Induced Colon Contractility in Diabetic Rats
Wynn Thein, Wah Wah Po, Dong Min Kim and Uy Dong Sohn*
Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
*E-mail: udsohn@cau.ac.kr
Tel: +82-2-820-5614, Fax: +82-2-826-8752
Received: October 30, 2019; Revised: December 24, 2019; Accepted: January 7, 2020; Published online: March 4, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Diabetes mellitus affects the colonic motility developing gastrointestinal symptoms, such as constipation. The aim of the study was to examine the role of intracellular signaling pathways contributing to colonic dysmotility in diabetes mellitus. To generate diabetes mellitus, the rats were injected by a single high dose of streptozotocin (65 mg/kg) intraperitoneally. The proximal colons from both normal and diabetic rats were contracted by applying an electrical field stimulation with pulse voltage of 40 V in amplitude and pulse duration of 1 ms at frequencies of 1, 2, 4, and 6 Hz. The muscle strips from both normal rats and rats with diabetes mellitus were pretreated with different antagonists and inhibitors. Rats with diabetes mellitus had lower motility than the control group. There were significant differences in the percentage of inhibition of contraction between normal rats and rats with diabetes mellitus after the incubation of tetrodotoxin (neuronal blocker), atropine (muscarinic receptor antagonist), prazosin (α1 adrenergic receptor antagonist), DPCPX (adenosine A1 receptor antagonist), verapamil (L-type Ca2+ channel blocker), U73122 (PLC inhibitor), ML-9 (MLCK inhibitor), udenafil (PDE5 inhibitor), and methylene blue (guanylate cyclase inhibitor). The protein expression of p-MLC and PDE5 were decreased in the diabetic group compared to the normal group. These results showed that the reduced colonic contractility resulted from the impaired neuronal conduction and decreased muscarinic receptor sensitivity, which resulted in decreased phosphorylation of MLC via MLCK, and cGMP activity through PDE5.
Keywords: Gastrointestinal motility, Electrical field stimulation, Colon, Diabetes mellitus


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