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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

Concentration-dependent increase in Isc across mucosa preparations from rat distal colon induced by serosal administration of nicotine (in the presence of tetrodotoxin). Values are given as increase in Isc (ΔIsc) above baseline just prior administration of the respective nicotine concentration and are means (filled circles) ± SEM (vertical lines), n = 6–8.
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fig03: Concentration-dependent increase in Isc across mucosa preparations from rat distal colon induced by serosal administration of nicotine (in the presence of tetrodotoxin). Values are given as increase in Isc (ΔIsc) above baseline just prior administration of the respective nicotine concentration and are means (filled circles) ± SEM (vertical lines), n = 6–8.

Mentions: The effect of DMPP was mimicked by nicotine (Fig.3). Nicotine evoked a concentration-dependent increase in Isc. For lower agonist concentrations (<10−4 mol/L), the serosal compartment was washed three times with the fivefold chamber volume before the next concentration was administered. Due to an apparent desensitization of the Isc response evoked by nicotine at higher concentrations, nicotine in concentrations ≥10−4 mol/L was administered only once to the same tissue. A maximal response was evoked at a concentration of 3 × 10−4 mol/L, which declined when the concentration was elevated to 10−3 mol/L probably reflecting desensitization as nicotinic receptors are well known to possess the ability to transform into the desensitized state after agonist binding without prior transition into the activated state (Giniatullin et al. 2005).


Novel aspects of cholinergic regulation of colonic ion transport.

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

Concentration-dependent increase in Isc across mucosa preparations from rat distal colon induced by serosal administration of nicotine (in the presence of tetrodotoxin). Values are given as increase in Isc (ΔIsc) above baseline just prior administration of the respective nicotine concentration and are means (filled circles) ± SEM (vertical lines), n = 6–8.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: Concentration-dependent increase in Isc across mucosa preparations from rat distal colon induced by serosal administration of nicotine (in the presence of tetrodotoxin). Values are given as increase in Isc (ΔIsc) above baseline just prior administration of the respective nicotine concentration and are means (filled circles) ± SEM (vertical lines), n = 6–8.
Mentions: The effect of DMPP was mimicked by nicotine (Fig.3). Nicotine evoked a concentration-dependent increase in Isc. For lower agonist concentrations (<10−4 mol/L), the serosal compartment was washed three times with the fivefold chamber volume before the next concentration was administered. Due to an apparent desensitization of the Isc response evoked by nicotine at higher concentrations, nicotine in concentrations ≥10−4 mol/L was administered only once to the same tissue. A maximal response was evoked at a concentration of 3 × 10−4 mol/L, which declined when the concentration was elevated to 10−3 mol/L probably reflecting desensitization as nicotinic receptors are well known to possess the ability to transform into the desensitized state after agonist binding without prior transition into the activated state (Giniatullin et al. 2005).

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