Signaling pathways underlying changes in the contractility of the stomach fundus smooth muscle in diabetic rats

Abstract

Dysfunction of gastrointestinal (GI) motility is a common complication in patients with diabetes mellitus (DM). Studies related to changes in fundus contraction induced by inhibitors in DM are not well known. Therefore, this study aimed to investigate the signaling pathways involved in the changes in the contraction of fundus smooth muscle obtained from control and DM rats. DM was induced by injecting streptozotocin (65 mg/kg) into Sprague–Dawley rats. The rats were sacrificed after 14 days. Fundus smooth muscle contraction was stimulated using electrical field stimulation (amplitude, 50 V; duration, 1 min; frequency, 2–20 Hz) and acetylcholine (0.1 mM). The inhibitor-mediated cell membrane was pre-treated with atropine, verapamil, methysergide, ketanserin, ondansetron, and GR 113808. Inhibitors related to intracellular signaling, such as U73122, chelerythrine, l-NNA, were also used. ML-9 and Y-27632 were identified as inhibitors of factors of myosin light chain (MLC). The contractility was observed to be lower in the DM group than in the control group. Further, the activities of phospholipase C (PLC), protein kinase C (PKC), and myosin light chain kinase (MLCK) were decreased in the DM group. DM reduced the activity of PLC, PKC, and MLCK, which resulted in a decrease in the contractility of the fundus smooth muscle. Therefore, our results present the mechanism of this DM-mediated GI disorder.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science, and Technology (NRF-2019R1F1A1062070).

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Correspondence to Uy Dong Sohn.

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Kim, D.M., Khing, T.M., Thein, W. et al. Signaling pathways underlying changes in the contractility of the stomach fundus smooth muscle in diabetic rats. Arch. Pharm. Res. 43, 666–675 (2020). https://doi.org/10.1007/s12272-020-01244-z

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Keywords

  • Diabetes mellitus
  • Fundus
  • Smooth muscle
  • PLC
  • MLCK