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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

Choline desensitizes the tissue against acetylcholine. Acetylcholine (10−3 mol/L) induces a long-lasting increase in Isc across mucosa–submucosa preparations under control conditions (A), which is desensitized by three prior administrations of choline (10−3 mol/L; B). Values are given as means (symbols) ± SEM (lines), n = 6–7. Line interruptions are caused by omission of time intervals in order to synchronize the tracings of individual records to the administration of drugs. For statistics, see Table2.
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fig10: Choline desensitizes the tissue against acetylcholine. Acetylcholine (10−3 mol/L) induces a long-lasting increase in Isc across mucosa–submucosa preparations under control conditions (A), which is desensitized by three prior administrations of choline (10−3 mol/L; B). Values are given as means (symbols) ± SEM (lines), n = 6–7. Line interruptions are caused by omission of time intervals in order to synchronize the tracings of individual records to the administration of drugs. For statistics, see Table2.

Mentions: In rat brain, the low-affinity stimulation of α7 nicotinic receptors by choline is thought to play mainly a modulatory role, as low concentrations of choline lead to a desensitization of the corresponding receptors (Alkondon et al. 1997). In order to investigate, whether a similar desensitization of cholinergic receptors might occur at colonic epithelium, tissues were desensitized to choline by three consecutive administrations of this agonist (10−3 mol/L). Indeed, the Isc evoked by a subsequent administration of acetylcholine (10−3 mol/L) was significantly attenuated compared to an untreated control (Fig.10). A pretreatment with choline reduced not only the amplitude of the Isc response, but also shortened the duration of the response (quantified as increase in Isc above baseline 10 min after administration of acetylcholine) significantly (P < 0.05). The desensitization of the acetylcholine response by choline was concentration-dependent (Table2).


Novel aspects of cholinergic regulation of colonic ion transport.

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

Choline desensitizes the tissue against acetylcholine. Acetylcholine (10−3 mol/L) induces a long-lasting increase in Isc across mucosa–submucosa preparations under control conditions (A), which is desensitized by three prior administrations of choline (10−3 mol/L; B). Values are given as means (symbols) ± SEM (lines), n = 6–7. Line interruptions are caused by omission of time intervals in order to synchronize the tracings of individual records to the administration of drugs. For statistics, see Table2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig10: Choline desensitizes the tissue against acetylcholine. Acetylcholine (10−3 mol/L) induces a long-lasting increase in Isc across mucosa–submucosa preparations under control conditions (A), which is desensitized by three prior administrations of choline (10−3 mol/L; B). Values are given as means (symbols) ± SEM (lines), n = 6–7. Line interruptions are caused by omission of time intervals in order to synchronize the tracings of individual records to the administration of drugs. For statistics, see Table2.
Mentions: In rat brain, the low-affinity stimulation of α7 nicotinic receptors by choline is thought to play mainly a modulatory role, as low concentrations of choline lead to a desensitization of the corresponding receptors (Alkondon et al. 1997). In order to investigate, whether a similar desensitization of cholinergic receptors might occur at colonic epithelium, tissues were desensitized to choline by three consecutive administrations of this agonist (10−3 mol/L). Indeed, the Isc evoked by a subsequent administration of acetylcholine (10−3 mol/L) was significantly attenuated compared to an untreated control (Fig.10). A pretreatment with choline reduced not only the amplitude of the Isc response, but also shortened the duration of the response (quantified as increase in Isc above baseline 10 min after administration of acetylcholine) significantly (P < 0.05). The desensitization of the acetylcholine response by choline was concentration-dependent (Table2).

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