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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

Stimulation of epithelial nicotinic receptors evokes an increase in Isc. Dimethylphenylpiperazinium (DMPP, 10−4 mol/L) induces an increase in Isc in the presence of tetrodotoxin (TTX; 10−6 mol/L) across mucosa preparations from rat distal colon (A), which was suppressed by preincubation with hexamethonium (10−5 mol/L; B). Values are given as means (black symbols) ± SEM (gray area), n = 6. Line interruptions are caused by omission of time intervals in order to synchronize the tracings of individual records to the administration of drugs.
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fig02: Stimulation of epithelial nicotinic receptors evokes an increase in Isc. Dimethylphenylpiperazinium (DMPP, 10−4 mol/L) induces an increase in Isc in the presence of tetrodotoxin (TTX; 10−6 mol/L) across mucosa preparations from rat distal colon (A), which was suppressed by preincubation with hexamethonium (10−5 mol/L; B). Values are given as means (black symbols) ± SEM (gray area), n = 6. Line interruptions are caused by omission of time intervals in order to synchronize the tracings of individual records to the administration of drugs.

Mentions: Ussing chamber experiments were performed with DMPP (10−4 mol/L), a nicotinic receptor agonist (Tapper and Lewand 1981), in order to investigate if there is functional evidence for the expression of nicotinic receptors in colonic epithelium. The experiments were carried out on mucosa preparations of rat distal colon (i.e., in the absence of the myenteric and the submucosal plexus) and in the continuous presence of the neurotoxin tetrodotoxin (10−6 mol/L) in order to prevent effects of DMPP (or nicotine) on enteric neurons of the mucosal plexus, which is still present in these preparations (Bridges et al. 1986). DMPP induced a transient, tetrodotoxin-resistant increase in Isc of 2.87 ± 1.00 μEq/h per cm2 (n = 6; Fig.2A), which was suppressed, when the tissue was pretreated with the nicotinic receptor antagonist hexamethonium (10−5 mol/L, Fig.2B).


Novel aspects of cholinergic regulation of colonic ion transport.

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

Stimulation of epithelial nicotinic receptors evokes an increase in Isc. Dimethylphenylpiperazinium (DMPP, 10−4 mol/L) induces an increase in Isc in the presence of tetrodotoxin (TTX; 10−6 mol/L) across mucosa preparations from rat distal colon (A), which was suppressed by preincubation with hexamethonium (10−5 mol/L; B). Values are given as means (black symbols) ± SEM (gray area), n = 6. Line interruptions are caused by omission of time intervals in order to synchronize the tracings of individual records to the administration of drugs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Stimulation of epithelial nicotinic receptors evokes an increase in Isc. Dimethylphenylpiperazinium (DMPP, 10−4 mol/L) induces an increase in Isc in the presence of tetrodotoxin (TTX; 10−6 mol/L) across mucosa preparations from rat distal colon (A), which was suppressed by preincubation with hexamethonium (10−5 mol/L; B). Values are given as means (black symbols) ± SEM (gray area), n = 6. Line interruptions are caused by omission of time intervals in order to synchronize the tracings of individual records to the administration of drugs.
Mentions: Ussing chamber experiments were performed with DMPP (10−4 mol/L), a nicotinic receptor agonist (Tapper and Lewand 1981), in order to investigate if there is functional evidence for the expression of nicotinic receptors in colonic epithelium. The experiments were carried out on mucosa preparations of rat distal colon (i.e., in the absence of the myenteric and the submucosal plexus) and in the continuous presence of the neurotoxin tetrodotoxin (10−6 mol/L) in order to prevent effects of DMPP (or nicotine) on enteric neurons of the mucosal plexus, which is still present in these preparations (Bridges et al. 1986). DMPP induced a transient, tetrodotoxin-resistant increase in Isc of 2.87 ± 1.00 μEq/h per cm2 (n = 6; Fig.2A), which was suppressed, when the tissue was pretreated with the nicotinic receptor antagonist hexamethonium (10−5 mol/L, Fig.2B).

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