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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

Nicotine induces a Ca2+-dependent Cl− secretion. The Isc induced by nicotine (10−4 mol/L, applied in the presence of tetrodotoxin) across mucosa preparations from rat distal colon was either tested under control conditions (open bars) or after ion substitution or in the presence of different inhibitors of the Ca2+ signaling pathway, respectively (solid bars). For the Cl−-free solution, Cl− was removed from the serosal and the mucosal compartment, for the Ca2+-free solution, Ca2+ was removed from the serosal compartment. Inhibitors: trifluoperazine (5 × 10−5 mol/L) and calmidazolium (5 × 10−7 mol/L). Values are given as increase in Isc (ΔIsc) above baseline just prior administration of nicotine and are means ± SEM; n = 6–10. *P < 0.05 vs. response evoked by nicotine in the respective control series.
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fig05: Nicotine induces a Ca2+-dependent Cl− secretion. The Isc induced by nicotine (10−4 mol/L, applied in the presence of tetrodotoxin) across mucosa preparations from rat distal colon was either tested under control conditions (open bars) or after ion substitution or in the presence of different inhibitors of the Ca2+ signaling pathway, respectively (solid bars). For the Cl−-free solution, Cl− was removed from the serosal and the mucosal compartment, for the Ca2+-free solution, Ca2+ was removed from the serosal compartment. Inhibitors: trifluoperazine (5 × 10−5 mol/L) and calmidazolium (5 × 10−7 mol/L). Values are given as increase in Isc (ΔIsc) above baseline just prior administration of nicotine and are means ± SEM; n = 6–10. *P < 0.05 vs. response evoked by nicotine in the respective control series.

Mentions: In order to find out if the nicotine-induced Isc is due to Cl− secretion, anion substitution experiments were performed. In the presence of Cl−, nicotine (10−4 mol/L) evoked an increase in Isc of 5.58 ± 0.97 μEq/h per cm2 (n = 8, Fig.5). However, after substitution of Cl− on both sides of the tissue with the impermeable anion gluconate, the increase in Isc was significantly reduced and only amounted to 0.86 ± 0.33 μEq/h per cm2 (P < 0.05 vs. control, n = 8).


Novel aspects of cholinergic regulation of colonic ion transport.

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

Nicotine induces a Ca2+-dependent Cl− secretion. The Isc induced by nicotine (10−4 mol/L, applied in the presence of tetrodotoxin) across mucosa preparations from rat distal colon was either tested under control conditions (open bars) or after ion substitution or in the presence of different inhibitors of the Ca2+ signaling pathway, respectively (solid bars). For the Cl−-free solution, Cl− was removed from the serosal and the mucosal compartment, for the Ca2+-free solution, Ca2+ was removed from the serosal compartment. Inhibitors: trifluoperazine (5 × 10−5 mol/L) and calmidazolium (5 × 10−7 mol/L). Values are given as increase in Isc (ΔIsc) above baseline just prior administration of nicotine and are means ± SEM; n = 6–10. *P < 0.05 vs. response evoked by nicotine in the respective control series.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: Nicotine induces a Ca2+-dependent Cl− secretion. The Isc induced by nicotine (10−4 mol/L, applied in the presence of tetrodotoxin) across mucosa preparations from rat distal colon was either tested under control conditions (open bars) or after ion substitution or in the presence of different inhibitors of the Ca2+ signaling pathway, respectively (solid bars). For the Cl−-free solution, Cl− was removed from the serosal and the mucosal compartment, for the Ca2+-free solution, Ca2+ was removed from the serosal compartment. Inhibitors: trifluoperazine (5 × 10−5 mol/L) and calmidazolium (5 × 10−7 mol/L). Values are given as increase in Isc (ΔIsc) above baseline just prior administration of nicotine and are means ± SEM; n = 6–10. *P < 0.05 vs. response evoked by nicotine in the respective control series.
Mentions: In order to find out if the nicotine-induced Isc is due to Cl− secretion, anion substitution experiments were performed. In the presence of Cl−, nicotine (10−4 mol/L) evoked an increase in Isc of 5.58 ± 0.97 μEq/h per cm2 (n = 8, Fig.5). However, after substitution of Cl− on both sides of the tissue with the impermeable anion gluconate, the increase in Isc was significantly reduced and only amounted to 0.86 ± 0.33 μEq/h per cm2 (P < 0.05 vs. control, n = 8).

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