Evaluation of the gastrointestinal motility

The evaluation of the gastrointestinal (GI) motility is useful to detect pathological conditions of the GI system, the therapeutic potential of drugs in motility disorders or potential drug side effects on motility or inflammation.

Current treatments are non-specific, focused on reducing motility or contractions of the GI tissues, often targeting the messengers (cyclic nucleotides cAMP and cGMP). Dr. Rehman’s group1 investigated one mechanism to regulate these messengers, specifically the phosphodiesterase (PDE) family of enzymes.

Targeting one PDE enzyme, Roflumilast, which has been shown to reduce inflammation in a cardio and renal context, Dr. Rehman’s team investigated GI applications, specifically antispasmodic effects on the small intestine. Using the emkaBATH4 to measure contractility, they show that spontaneous contractions are inhibited using Roflumilast similar to the known calcium blocker agent, Verapamil.

Spontaneous Contractions comparing Roflumilast (A) and Verapamil (B) for their inhibitory effects
Figure 1 Spontaneous Contractions comparing Roflumilast (A) and Verapamil (B) for their inhibitory effects

Further testing using the emkaBATH4 against carbachol (CCh) induced contractions, showed a dose-dependent inhibition with Roflumilast, similar to Papavarine, a common treatment for smooth muscle spasms.

2 inhibition of carbahol-induced contractions comparing Roflumilast(A) and Papaverine(B)
Figure 2 inhibition of carbahol-induced contractions comparing Roflumilast(A) and Papaverine(B)

Results show that Roflumilast acts in a similar manner to current treatments, suggesting that it may be a valuable therapeutic agent in an antispasmodic capacity.

Tissue bath systems and their contractility outcomes act as a bridge between whole animal studies and high throughput single receptor cell-based screening tools. These outcomes complement each other, providing a deeper insight into potential mechanisms and therapeutics, without confounding effects of neuronal and hormonal influences.

References

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