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The cholinergic response is increased in isolated ileum from gastroschisis rat model
Aline Cristina Régis1, Julio Alejandro Rojas-Moscoso, Frances Lilian Lanhellas Gonçalves
1Department of Surgery, School of Medical Sciences, State University of Campinas-UNICAMP, Campinas, SP, Brazil.
Insights
Infants with gastroschisis (G) show reduced bowel motility. Studies reveal increased ileum reactivity and M3 receptor expression in fetal rats with experimental gastroschisis, suggesting an adaptive supersensitivity.
Area of Science:
- Developmental biology
- Gastroenterology
- Pharmacology
Background:
- Gastroschisis (G) in newborns leads to significant morbidity and prolonged hospitalization.
- Bowel hypomotility in gastroschisis is attributed to chronic exposure to amniotic fluid.
- Understanding fetal bowel adaptation is crucial for improving infant outcomes.
Purpose of the Study:
- To investigate the functional reactivity of the isolated ileum in a rat model of experimental gastroschisis.
- To assess changes in muscarinic receptor expression in the context of gastroschisis.
Main Methods:
- Surgical creation of gastroschisis in fetal rats at 18.5 days of gestation.
- Assessment of isolated ileum contractility using methacholine and electrical field stimulation (EFS).
- Quantification of M3 receptor protein expression via western blot analysis.
Main Results:
- Spontaneous ileum contractions (frequency and amplitude) were significantly decreased in the gastroschisis group.
- Methacholine-induced contractions and EFS-induced contractions were significantly higher in gastroschisis ileum.
- Increased M3 receptor protein expression was observed in the gastroschisis group.
Conclusions:
- Fetal gastroschisis is associated with reduced spontaneous ileum contractions.
- Ileum exhibits enhanced contractile responses to cholinergic stimulation and EFS in gastroschisis.
- These findings suggest an adaptive supersensitivity to cholinergic stimuli mediated by increased M3 receptor expression in gastroschisis.
Introduction:
Babies with gastroschisis (G) have high morbidity rate and long hospital stay due to bowel hypomotility caused by chronic exposure of the bowel to the amniotic fluid. Our aim was to evaluate the reactivity of isolated ileum in fetal rats selected for experimental gastroschisis.
Method:
G was surgically created at 18.5 days of gestation (term = 22 days). Concentration-dependent curve to the muscarinic agonist methacholine (1-30 μM) and contractions induced by electrical field stimulation (EFS, 1-16 Hz, 50 V, 1 ms) were carried out in isolated ileum of groups control (C), sham (S) and gastroschisis (G) (n = 30). Protein expression for M(3) was assessed by western blot analysis.
Results:
The frequency and amplitude of spontaneous contractions were decreased in G (p < 0.001). Methacholine produced concentration-dependent contractions being the maximal response values higher in G (p < 0.01). EFS-induced frequency-dependent contractions showed 1.8 times higher in G as well as an increase of M(3) expression.
Conclusion:
The frequency and the amplitude of rhythmic contractions were reduced along with an increase in the contraction induced by mucarinic agonist and by EFS in G. These results suggest the occurrence of an adaptative supersensitivity to cholinergic response via increases in the protein expression for M(3) receptor.
