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Published on: December 10, 2016
Clostridium difficile toxins impact on rat colon smooth muscle reactivity
Petar Vassilev1, Ekaterina Zaytseva1, Raina Ardasheva1
1Medical University of Plovdiv, Plovdiv, Bulgaria.
Aim:
The present study was conducted in an attempt to find possible direct mechanisms of action of Clostridium difficile toxins A and B (TCdA and TCdB) on contractility of isolated rat intestinal smooth muscles, as the contractive pathways affected by the toxins and responsible for motility disorders remain unclear.
Materials And Methods:
Adult male Wistar rats were used in our experiments. Longitudinal smooth muscle (SM) preparations of proximal colon were isolated and their contractile activity was isometrically registered. The samples were mounted in tissue baths and exogenously treated with acetylcholine (ACh), serotonin (5-HT), dopamine, norepinephrine, TCdA and TCdB. The potential of TCdA and TCdB to affect the action of these mediators on SM activity was examined.
Results:
The experiments have shown that exciting action of ACh and 5-HT on colonic contractility is enhanced by TCdA rather than TCdB. Conversely, relaxing effect of dopamine and norepinephrine on contractile activity of colonic SM is under impact of TCdB but not TcdA. TCdA has a stronger direct effect on in vitro SM sensitivity to ACh and 5-HT than TCdB.
Conclusions:
TCdA and TCdB affect directly the contractile reactivity of isolated rat colon smooth muscle. TCdA has a stronger direct effect on smooth muscle sensitivity to acetylcholine and 5-HT than TCdB. Such a trend has not been established for dopamine and norepinephrine.
Insights
Clostridium difficile toxins A and B (TcdA and TcdB) directly impact rat colon smooth muscle contractility. TcdA enhances responses to acetylcholine and serotonin, while TcdB influences dopamine and norepinephrine effects.
Area of Science:
- Gastroenterology
- Pharmacology
- Microbiology
Background:
- Clostridium difficile toxins A and B (TcdA, TcdB) are key virulence factors.
- Mechanisms underlying toxin-induced motility disorders are not fully understood.
Purpose of the Study:
- Investigate direct effects of TcdA and TcdB on isolated rat intestinal smooth muscle contractility.
- Elucidate toxin-specific modulation of neurotransmitter and neuromodulator actions.
Main Methods:
- Isolated longitudinal smooth muscle preparations from rat proximal colon.
- Isometric contractile activity measurement.
- Exogenous application of acetylcholine, serotonin, dopamine, norepinephrine, TcdA, and TcdB.
Main Results:
- TcdA significantly enhanced acetylcholine and serotonin-induced contractions.
- TcdB modulated dopamine and norepinephrine-induced relaxations.
- TcdA demonstrated a more potent effect on smooth muscle sensitivity to acetylcholine and serotonin compared to TcdB.
Conclusions:
- TcdA and TcdB directly alter rat colon smooth muscle contractility.
- TcdA exhibits a stronger direct influence on acetylcholine and serotonin sensitivity.
- Distinct effects of TcdA and TcdB on smooth muscle responses to various mediators were observed.
