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Cholinergic-induced anion secretion in murine jejunal enteroids involves synergy between muscarinic and nicotinic pathways.
Am J Physiol Cell Physiol. 2020 Aug 01; 319(2):C321-C330.AJ

Abstract

Acetylcholine induces robust electrogenic anion secretion in mammalian intestine and it has long been hypothesized that it mediates the epithelial response through the M3 and, to a lesser extent, the M1 muscarinic receptors in the mouse. However, nicotinic receptors have recently been identified in intestinal enterocytes by quantitative real-time (qRT)-PCR/RNAseq, although any direct influence on intestinal transport has not been identified. We tested the hypothesis that cholinergic-induced anion secretion in the intestine is a result of both muscarinic and nicotinic pathways that are intrinsic to the intestinal epithelia. We developed a method to generate mouse jejunal enteroid monolayers which were used to measure active electrogenic anion secretion by the Ussing chamber/voltage-clamp technique. Here, we show that the cholinergic agonist carbachol (CCh) and the muscarinic agonist bethanechol (BCh) stimulate short-lived, concentration-dependent anion secretion in the epithelial cell-only enteroid monolayers. The muscarinic antagonist atropine completely inhibited CCh- and BCh-induced secretion, while the nicotinic antagonist hexamethonium reduced the CCh response by ~45%. While nicotine alone did not alter anion secretion, it increased the BCh-induced increase in short-circuit current in a concentration-dependent manner; this synergy was prevented by pretreatment with hexamethonium. In addition to being sensitive to hexamethonium, monolayers express both classes of cholinergic receptor by qRT-PCR, including 13 of 16 nicotinic receptor subunits. Our findings indicate that an interaction between muscarinic and nicotinic agonists synergistically stimulates anion secretion in mouse jejunal epithelial cells and identify a role for epithelial nicotinic receptors in anion secretion.

Authors+Show Affiliations

Department of Cellular and Molecular Physiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland.Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland.Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland.Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland.Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland.Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland.Department of Cellular and Molecular Physiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32551856

Citation

Johnson, Kelli, et al. "Cholinergic-induced Anion Secretion in Murine Jejunal Enteroids Involves Synergy Between Muscarinic and Nicotinic Pathways." American Journal of Physiology. Cell Physiology, vol. 319, no. 2, 2020, pp. C321-C330.
Johnson K, Yin J, In JG, et al. Cholinergic-induced anion secretion in murine jejunal enteroids involves synergy between muscarinic and nicotinic pathways. Am J Physiol, Cell Physiol. 2020;319(2):C321-C330.
Johnson, K., Yin, J., In, J. G., Kulkarni, S., Pasricha, P., Tse, C. M., & Donowitz, M. (2020). Cholinergic-induced anion secretion in murine jejunal enteroids involves synergy between muscarinic and nicotinic pathways. American Journal of Physiology. Cell Physiology, 319(2), C321-C330. https://doi.org/10.1152/ajpcell.00179.2020
Johnson K, et al. Cholinergic-induced Anion Secretion in Murine Jejunal Enteroids Involves Synergy Between Muscarinic and Nicotinic Pathways. Am J Physiol, Cell Physiol. 2020 Aug 1;319(2):C321-C330. PubMed PMID: 32551856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholinergic-induced anion secretion in murine jejunal enteroids involves synergy between muscarinic and nicotinic pathways. AU - Johnson,Kelli, AU - Yin,Jianyi, AU - In,Julie G, AU - Kulkarni,Subhash, AU - Pasricha,Pankaj, AU - Tse,Chung Ming, AU - Donowitz,Mark, Y1 - 2020/06/17/ PY - 2020/6/20/pubmed PY - 2020/6/20/medline PY - 2020/6/20/entrez KW - anion secretion KW - cholinergic KW - enteroids KW - monolayers KW - nicotinic SP - C321 EP - C330 JF - American journal of physiology. Cell physiology JO - Am. J. Physiol., Cell Physiol. VL - 319 IS - 2 N2 - Acetylcholine induces robust electrogenic anion secretion in mammalian intestine and it has long been hypothesized that it mediates the epithelial response through the M3 and, to a lesser extent, the M1 muscarinic receptors in the mouse. However, nicotinic receptors have recently been identified in intestinal enterocytes by quantitative real-time (qRT)-PCR/RNAseq, although any direct influence on intestinal transport has not been identified. We tested the hypothesis that cholinergic-induced anion secretion in the intestine is a result of both muscarinic and nicotinic pathways that are intrinsic to the intestinal epithelia. We developed a method to generate mouse jejunal enteroid monolayers which were used to measure active electrogenic anion secretion by the Ussing chamber/voltage-clamp technique. Here, we show that the cholinergic agonist carbachol (CCh) and the muscarinic agonist bethanechol (BCh) stimulate short-lived, concentration-dependent anion secretion in the epithelial cell-only enteroid monolayers. The muscarinic antagonist atropine completely inhibited CCh- and BCh-induced secretion, while the nicotinic antagonist hexamethonium reduced the CCh response by ~45%. While nicotine alone did not alter anion secretion, it increased the BCh-induced increase in short-circuit current in a concentration-dependent manner; this synergy was prevented by pretreatment with hexamethonium. In addition to being sensitive to hexamethonium, monolayers express both classes of cholinergic receptor by qRT-PCR, including 13 of 16 nicotinic receptor subunits. Our findings indicate that an interaction between muscarinic and nicotinic agonists synergistically stimulates anion secretion in mouse jejunal epithelial cells and identify a role for epithelial nicotinic receptors in anion secretion. SN - 1522-1563 UR - https://www.unboundmedicine.com/medline/citation/32551856/Cholinergic-induced_anion_secretion_in_murine_jejunal_enteroids_involves_synergy_between_muscarinic_and_nicotinic_pathways L2 - https://journals.physiology.org/doi/10.1152/ajpcell.00179.2020?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
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