Functional characterization of muscarinic receptor subtypes in human duodenal secretion
- 26 August 2004
- journal article
- Published by Wiley in Acta Physiologica Scandinavica
- Vol. 182 (1) , 63-68
- https://doi.org/10.1111/j.1365-201x.2004.01301.x
Abstract
Aim: Acetylcholine (ACh) stimulates ion secretion in the small intestine and colon. The purpose of the present study was to characterize the ACh‐induced electrogenic ion transport in human duodenum and determine the muscarinic receptor subtypes functionally involved.Methods: Biopsies from the second part of duodenum were obtained from 28 patients during endoscopy. Biopsies were mounted in modified Ussing chambers with air‐suction for measurements of short‐circuit current by a previously validated technique. Short‐circuit current was measured after application of chloride/bicarbonate transport inhibitors bumetanide, 4‐acetamido‐4′‐isothiocyanostilbene‐2,2′‐disulfonic acid (SITS), diphenylamine‐2‐carboxylate (DPC), and acetazolamide. 4‐diphenylacetoxy‐N‐methylpiperidine methiodide (4‐DAMP) and two mamba toxins MT3 and MT7 were used to characterize the mAChR receptor subtypes involved. The effects of transport inhibitors and receptor antagonists were measured by comparing two consecutive responses of ACh on short‐circuit current in the same biopsy specimen.Results: Bumetanide and 4‐DAMP significantly inhibited ACh‐induced short‐circuit current, whereas SITS, DPC, acetazolamide, mamba toxin MT3, and mamba toxin MT7 all failed to show any significant effect.Conclusion: In conclusion, our results indicate that muscarinic receptor subtype M3 acts as the main mediator of bumetanide‐sensitive ACh‐induced secretion in human duodenum.Keywords
This publication has 20 references indexed in Scilit:
- Muscarinic M2 Receptor Stimulation of Cav1.2b Requires Phosphatidylinositol 3-Kinase, Protein Kinase C, and c-SrcCirculation Research, 2004
- Novel modified Ussing chamber for the study of absorption and secretion in human endoscopic biopsiesActa Physiologica Scandinavica, 2001
- Snake toxins with high selectivity for subtypesof muscarinic acetylcholine receptorsBiochimie, 2000
- The muscarinic M5 receptor: a silent or emerging subtype?British Journal of Pharmacology, 2000
- Electrogenic Ion Transport in Duodenum, an Aid in Cystic Fibrosis DiagnosisScandinavian Journal of Gastroenterology, 2000
- Electrogenic Ion Transport along the Human Duodenum in ChildhoodScandinavian Journal of Gastroenterology, 1997
- Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers.Gut, 1995
- Synthesis, muscarinic blocking activity and molecular modeling studies of 4-DAMP-related compoundsBioorganic & Medicinal Chemistry, 1995
- Cholinergic neurons and muscarinic receptors regulate anion secretion in pig distal jejunumEuropean Journal of Pharmacology, 1991
- Muscarinic Receptor SubtypesNew England Journal of Medicine, 1989