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Novel aspects of cholinergic regulation of colonic ion transport.

Bader S, Diener M - Pharmacol Res Perspect (2015)

Bottom Line: As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I sc was examined.Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion.Thus the cholinergic regulation of colonic ion transport - up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors - is more complex than previously assumed.

View Article: PubMed Central - PubMed

Affiliation: Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen Giessen, Germany.

ABSTRACT
Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (I sc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I sc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport - up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors - is more complex than previously assumed.

No MeSH data available.


Related in: MedlinePlus

Histochemical detection of acetylcholinesterase activity in rat colonic epithelium. (A) Lower part: muscularis propria; upper part: surface area of the colonic epithelium. For the negative control (B), acetylthiocholine in the incubation medium was omitted. Typical results from three independent experiments; scale bars: 50 μm.
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fig06: Histochemical detection of acetylcholinesterase activity in rat colonic epithelium. (A) Lower part: muscularis propria; upper part: surface area of the colonic epithelium. For the negative control (B), acetylthiocholine in the incubation medium was omitted. Typical results from three independent experiments; scale bars: 50 μm.

Mentions: Acetylcholinesterase has been detected in mucosal scrapings of the large intestine of different mammals (Sine et al. 1988), and the end product of the esterase reaction, choline, is known to exert affinity for different nicotinic receptors (Alkondon et al. 1997; Alkondon and Albuquerque 2006). In order to test the ability of the colonic epithelium to cleave acetylcholine and thus produce choline, which might potentially act at nicotinic receptors within the tissue, an enzyme-histochemical staining for acetylcholinesterase was performed. As can be seen in Figure6, the colonic epithelium expresses an acetylcholinesterase activity. The reaction product was observed all over the crypt axis, especially in the middle part of the crypts.


Novel aspects of cholinergic regulation of colonic ion transport.

Bader S, Diener M - Pharmacol Res Perspect (2015)

Histochemical detection of acetylcholinesterase activity in rat colonic epithelium. (A) Lower part: muscularis propria; upper part: surface area of the colonic epithelium. For the negative control (B), acetylthiocholine in the incubation medium was omitted. Typical results from three independent experiments; scale bars: 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492755&req=5

fig06: Histochemical detection of acetylcholinesterase activity in rat colonic epithelium. (A) Lower part: muscularis propria; upper part: surface area of the colonic epithelium. For the negative control (B), acetylthiocholine in the incubation medium was omitted. Typical results from three independent experiments; scale bars: 50 μm.
Mentions: Acetylcholinesterase has been detected in mucosal scrapings of the large intestine of different mammals (Sine et al. 1988), and the end product of the esterase reaction, choline, is known to exert affinity for different nicotinic receptors (Alkondon et al. 1997; Alkondon and Albuquerque 2006). In order to test the ability of the colonic epithelium to cleave acetylcholine and thus produce choline, which might potentially act at nicotinic receptors within the tissue, an enzyme-histochemical staining for acetylcholinesterase was performed. As can be seen in Figure6, the colonic epithelium expresses an acetylcholinesterase activity. The reaction product was observed all over the crypt axis, especially in the middle part of the crypts.

Bottom Line: As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I sc was examined.Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion.Thus the cholinergic regulation of colonic ion transport - up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors - is more complex than previously assumed.

View Article: PubMed Central - PubMed

Affiliation: Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen Giessen, Germany.

ABSTRACT
Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (I sc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I sc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport - up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors - is more complex than previously assumed.

No MeSH data available.


Related in: MedlinePlus