title: Effects of Buscopan on human gastrointestinal smooth muscle activity in an ex vivo model: Are there any differences for various sections?
abstract: Hyoscine butylbromide (Buscopan ®) is clinically used as an anticholinergic antispasmodic for the treatment of abdominal cramping or visceral pain associated with cramps. However, the spasmolytic efficacy on contractile activity of human gastrointestinal smooth muscle from various sections remains unclear. We aimed to investigate the potentially selective actions of Buscopan on different bowel segments, as well as muscular layers and contractile states. Human smooth muscle tissues of the esophagus, gastric corpus and antrum, jejunum, ileum and colon were obtained. Isometric measurements of circular and longitudinal muscle strips were performed to determine effects of Buscopan on spontaneous activity and induced-contractions by 30mM KCl, 10μM bethanechol and electrical field stimulation (EFS). Buscopan concentration-dependently (10(-9)-10(-5)M) inhibited smooth muscle activity, particularly in spasticity evoked by bethanechol and EFS but not high K(+). The inhibiting effects were mainly responsible for the antagonism on muscarinic M2 and M3 receptors (IC50 values: 3.1×10(-5)M vs. 0.9×10(-5)M). The sensitivity toward Buscopan revealed a tendency of increasing from the esophagus, gastric corpus and antrum to the colon, jejunum and ileum. There was a reversed gradient of mRNA and protein expression of muscarinic M2 and M3 receptors from the blocking effects of Buscopan, which could be ascribed to the fact that a higher concentration of Buscopan was needed to antagonize the spastic contraction to reach the equipotent inhibitory rate in the region with higher muscarinic receptor activity. The findings of different inhibitory effectiveness on various parts of the gastrointestinal tract provide a potential guideline for the clinical application.
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China. Electronic address: houxh@medmail.com.cn.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Hou
mesh_terms: D000328:Adult; D002086:Butylscopolammonium Bromide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D024510:Muscle Development / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects; D009928:Organ Specificity; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D055815:Young Adult
chemical_list: D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D002086:Butylscopolammonium Bromide
keywords: 4-diphenylacetoxy-N-methylpiperidine methiodide (PubChem CID: 3014059); Abdominal cramps; Antispasmodics; Bethanechol chloride (PubChem CID: 11548); Buscopan; Gastrointestinal smooth muscle; Hexamethonium (PubChem CID: 3604); Hyoscine butylbromide; Methoctramine hydrate (PubChem CID: 71308551)