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Signaling pathways underlying changes in the contractility of the stomach fundus smooth muscle in diabetic rats.
Arch Pharm Res. 2020 Jun; 43(6):666-675.AP

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.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea. udsohn@cau.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32607942

Citation

Kim, Dong Min, et al. "Signaling Pathways Underlying Changes in the Contractility of the Stomach Fundus Smooth Muscle in Diabetic Rats." Archives of Pharmacal Research, vol. 43, no. 6, 2020, pp. 666-675.
Kim DM, Khing TM, Thein W, et al. Signaling pathways underlying changes in the contractility of the stomach fundus smooth muscle in diabetic rats. Arch Pharm Res. 2020;43(6):666-675.
Kim, D. M., Khing, T. M., Thein, W., Choi, W. S., Shin, C. Y., & Sohn, U. D. (2020). Signaling pathways underlying changes in the contractility of the stomach fundus smooth muscle in diabetic rats. Archives of Pharmacal Research, 43(6), 666-675. https://doi.org/10.1007/s12272-020-01244-z
Kim DM, et al. Signaling Pathways Underlying Changes in the Contractility of the Stomach Fundus Smooth Muscle in Diabetic Rats. Arch Pharm Res. 2020;43(6):666-675. PubMed PMID: 32607942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Signaling pathways underlying changes in the contractility of the stomach fundus smooth muscle in diabetic rats. AU - Kim,Dong Min, AU - Khing,Tin Myo, AU - Thein,Wynn, AU - Choi,Won Seok, AU - Shin,Chang Yell, AU - Sohn,Uy Dong, Y1 - 2020/06/30/ PY - 2020/04/02/received PY - 2020/06/25/accepted PY - 2020/7/2/pubmed PY - 2020/7/2/medline PY - 2020/7/2/entrez KW - Diabetes mellitus KW - Fundus KW - MLCK KW - PLC KW - Smooth muscle SP - 666 EP - 675 JF - Archives of pharmacal research JO - Arch. Pharm. Res. VL - 43 IS - 6 N2 - 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. SN - 0253-6269 UR - https://www.unboundmedicine.com/medline/citation/32607942/Signaling_pathways_underlying_changes_in_the_contractility_of_the_stomach_fundus_smooth_muscle_in_diabetic_rats L2 - https://dx.doi.org/10.1007/s12272-020-01244-z DB - PRIME DP - Unbound Medicine ER -
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