bis -(p-hydroxyphenyl)-pyridyl-2-methane (BHPM)-the active metabolite of the laxatives bisacodyl and sodium picosulfate-enhances contractility and secretion in human intestine in vitro
| Autor: | Florian Zeller, Ihsan Ekin Demir, Michael Schemann, Dagmar Krueger, G.O. Ceyhan |
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| Rok vydání: | 2018 |
| Předmět: |
Bisacodyl
Sodium picosulfate Physiology medicine.medical_treatment Laxative Pharmacology Contractility 03 medical and health sciences chemistry.chemical_compound Muscle tone Organ Culture Techniques 0302 clinical medicine Intestine Small Organometallic Compounds medicine Humans Channel blocker Citrates Intestine Large Benzhydryl Compounds Intestinal Mucosa Ussing chamber Endocrine and Autonomic Systems Gastroenterology Iberiotoxin medicine.anatomical_structure chemistry Laxatives Picolines 030211 gastroenterology & hepatology Gastrointestinal Motility 030217 neurology & neurosurgery Muscle Contraction medicine.drug |
| Zdroj: | Neurogastroenterology & Motility. 30:e13311 |
| ISSN: | 1350-1925 |
| Popis: | Background Stimulant laxatives are widely used to treat constipation. We investigated in human small and large intestinal preparations the effects of bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), the active metabolite of the laxatives bisacodyl and sodium picosulfate on smooth muscle tone and epithelial secretion. Methods Circular and longitudinal muscle tone of small or large intestinal preparations were recorded with isometric force transducers. Epithelial ion flux (ISC ) and tissue resistance was measured with Ussing chamber technique after apical and basolateral BHPM application to large intestinal mucosa/submucosa preparations. Studies were performed in macroscopically normal specimens from 79 patients. Key results BHPM concentration-dependently (0.5-5 μM) increased the tone of circular and longitudinal muscle from small to large intestine. The effect was strongest in large intestinal longitudinal muscle and smallest in small intestinal circular muscle. Increase in muscle tone was prevented by the L-type Ca++ channel blocker nifedipine but insensitive to the nerve blocker tetrodotoxin. Apical or basolateral BHPM concentration-dependently decreased or increased ISC, respectively. The KCa 1.1 (BK) channel blocker iberiotoxin reversed apical ISC decrease whereas tetrodotoxin reversed basolateral ISC increase. BHPM had no effect on tissue resistance or nerve-mediated secretory or muscle response with one exception: at the highest concentration basolateral BHPM reduced nerve-mediated secretion. Conclusions and interferences BHPM enhanced mucosal secretion and muscle contractility. Results suggested that the laxative effect of BHPM was a consequence of the increase in muscle tone as well as an increased K+ secretion when acting luminally and a nerve-driven Cl- and HCO3- secretion once acting basolaterally after absorption. |
| Databáze: | OpenAIRE |
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