Shugan Decoction Alleviates Colonic Dysmotility in Female SERT-Knockout Rats by Decreasing M3 Receptor Expression

Yinshu Wang; Ying Dong; Enkang Wang; Yangyang Meng; Zijuan Bi; Shuai Sun; Chaochao Zhang; Haiting Fan; Jianye Yuan

doi:10.3389/fphar.2020.01082

Shugan Decoction Alleviates Colonic Dysmotility in Female SERT-Knockout Rats by Decreasing M₃ Receptor Expression

Front Pharmacol. 2020 Sep 11:11:01082. doi: 10.3389/fphar.2020.01082. eCollection 2020.

Authors

Yinshu Wang¹, Ying Dong², Enkang Wang¹, Yangyang Meng¹, Zijuan Bi¹, Shuai Sun³, Chaochao Zhang⁴, Haiting Fan⁴, Jianye Yuan¹

Affiliations

¹ Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ Laboratory Animal Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Background: Irritable bowel syndrome (IBS) is a functional gut disease characterized by visceral hypersensitivity and gut motor dysfunction. Serotonin (5-hydroxytryptamine, 5-HT) is an important enteric neurotransmitter. High levels of 5-HT aggravate IBS symptoms. The serotonin reuptake transporter (SERT) is a membrane-embedded transporter involved in IBS pathogenesis that plays an important role in regulating 5-HT signaling.

Aim: We investigated whether gut motor function was altered in SERT-knockout (SERT-KO) rats. Additionally, we sought to determine whether Shugan decoction (SGD), a clinically experienced prescription for the treatment of IBS, exerts regulatory effects on intestinal motility in SERT-KO rats, and attempted to identify the mechanisms involved.

Method: SERT-KO rats were produced by transcription activator-like effector nuclease (TALEN) technology. Fecal pellet output was measured for ten consecutive days to estimate distal colonic motility. Small intestinal motility was measured by charcoal-meal experiments. The colonic and small intestinal muscle contractile activities were measured by organ bath study. Western blot was used to analyze the muscarinic receptor expression in colon tissue.

Result: Compared with that in wild-type (WT) rats, the defecation amount, amplitude of spontaneous contraction, and the tension of ACh-induced contraction of colonic longitudinal smooth muscle in SERT-KO rats were significantly increased. The expression of muscarinic receptor subtype-3 (M₃R) in the colons of SERT-KO rats was also elevated. SGD can decrease defecation of SERT-KO rats. Moreover, SGD reduced the amplitude of spontaneous contraction, the frequency and tension of ACh-induced contraction of colonic longitudinal smooth muscle, and the expression of M₃R in the colon in SERT-KO rats.

Conclusions: SERT-KO rats showed increased defecation accompanied by enhanced colonic motility and M₃R expression. The findings suggest that SGD modifies colonic dysmotility and reduces defecation in SERT-KO rats by down-regulating M₃R expression in the colon.

Keywords: Shugan decoction; intestinal motility; irritable bowel syndrome; muscarinic receptor; rats; serotonin reuptake transporter.