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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 ╬▒2, ╬▒4, ╬▒5, ╬▒6, ╬▒7, ╬▒10, and ╬▓4 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

Concentration-dependent increase in Isc across mucosaÔÇôsubmucosa preparations from rat distal colon induced by serosal administration of choline (filled circles, black solid line), Because of a desensitization, each tissue was treated with only one concentration of choline. Values are given as increase in Isc (╬öIsc) above baseline just prior administration of the respective agonist concentration and are means (symbols)┬á┬▒┬áSEM (vertical lines), n┬á=┬á6.
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fig07: Concentration-dependent increase in Isc across mucosaÔÇôsubmucosa preparations from rat distal colon induced by serosal administration of choline (filled circles, black solid line), Because of a desensitization, each tissue was treated with only one concentration of choline. Values are given as increase in Isc (╬öIsc) above baseline just prior administration of the respective agonist concentration and are means (symbols)┬á┬▒┬áSEM (vertical lines), n┬á=┬á6.

Mentions: Thus we asked the question whether choline might stimulate nicotinic receptors in the colonic wall. As not only the epithelium (Fig.6) but also enteric nerves (Mestres et┬áal. 1992) express high acetylcholinesterase activity, choline might be produced in close vicinity of enteric neurons, too. Therefore, for the Ussing chamber experiments with choline, a mucosaÔÇôsubmucosa preparation was used with an intact submucosal plexus in order not to overlook possible effects of choline at neuronal nicotinic receptors. Choline (10Ôłĺ3┬ámol/L to 10Ôłĺ2┬ámol/L) evoked a concentration-dependent increase in Isc (Fig.7). Because a strong desensitization was observed after repeated administration of the agonist to the same tissue (data not shown), choline was administered only once to the same tissue. Desensitization might also explain why the Isc response declined at the highest concentration tested in the concentrationÔÇôresponse curve experiments (Fig.7).


Novel aspects of cholinergic regulation of colonic ion transport.

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

Concentration-dependent increase in Isc across mucosaÔÇôsubmucosa preparations from rat distal colon induced by serosal administration of choline (filled circles, black solid line), Because of a desensitization, each tissue was treated with only one concentration of choline. Values are given as increase in Isc (╬öIsc) above baseline just prior administration of the respective agonist concentration and are means (symbols)┬á┬▒┬áSEM (vertical lines), n┬á=┬á6.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig07: Concentration-dependent increase in Isc across mucosaÔÇôsubmucosa preparations from rat distal colon induced by serosal administration of choline (filled circles, black solid line), Because of a desensitization, each tissue was treated with only one concentration of choline. Values are given as increase in Isc (╬öIsc) above baseline just prior administration of the respective agonist concentration and are means (symbols)┬á┬▒┬áSEM (vertical lines), n┬á=┬á6.
Mentions: Thus we asked the question whether choline might stimulate nicotinic receptors in the colonic wall. As not only the epithelium (Fig.6) but also enteric nerves (Mestres et┬áal. 1992) express high acetylcholinesterase activity, choline might be produced in close vicinity of enteric neurons, too. Therefore, for the Ussing chamber experiments with choline, a mucosaÔÇôsubmucosa preparation was used with an intact submucosal plexus in order not to overlook possible effects of choline at neuronal nicotinic receptors. Choline (10Ôłĺ3┬ámol/L to 10Ôłĺ2┬ámol/L) evoked a concentration-dependent increase in Isc (Fig.7). Because a strong desensitization was observed after repeated administration of the agonist to the same tissue (data not shown), choline was administered only once to the same tissue. Desensitization might also explain why the Isc response declined at the highest concentration tested in the concentrationÔÇôresponse curve experiments (Fig.7).

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 ╬▒2, ╬▒4, ╬▒5, ╬▒6, ╬▒7, ╬▒10, and ╬▓4 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