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Differential changes in ACh-, motilin-, substance P-, and K(+)-induced contractility in rabbit colitis
I Depoortere1, G Van Assche, T Thijs
1Gut Hormone Laboratory, Department of Pathophysiology, Katholieke Universiteit Leuven, Louvain B-3000, Belgium.
Abstract:
To test the hypothesis that the changes in intestinal contractility, which accompany inflammation of the gut, are agonist specific, we compared the response of inflamed strips to substance P (SP), motilin, ACh, and K(+) as a function of time. In parallel experiments, changes in the general mechanical properties (passive tension, optimal stretch) of the colitic tissue were evaluated. Colitis was induced by trinitrobenzenesulfonic acid, and rabbits were killed after 1, 2, 3, 5, or 8 days. Passive tension was increased starting from day 2 until day 8, and maximal active tension (T(max)) was generated at less stretch from day 5. A 50% decrease in T(max) was observed for ACh and K(+) between days 2 and 3 and for motilin and SP between days 3 and 5. For all compounds, T(max) returned to normal after 8 days. The pEC(50) value (negative logarithm of the concentration that induces 50% of the maximal contractile activity) for ACh was increased from day 3 until day 8 and for SP at day 3, whereas for motilin it was decreased at day 1. The changes in passive tension and optimal stretch indicate generalized structural alterations of smooth muscle tissue. However, the different time profiles of the changes in active tension and contractile potency for different contractile agents suggest that inflammation specifically affects receptor-mediated mechanisms.
Insights
Gut inflammation alters intestinal muscle responses in a specific way, affecting different signaling molecules (agonists) differently over time. These changes in contractility and potency suggest targeted impacts on receptor mechanisms during colitis.
Area of Science:
- Gastroenterology
- Physiology
- Pharmacology
Background:
- Intestinal inflammation, such as colitis, is known to alter gut motility.
- The specific mechanisms by which inflammation affects intestinal contractility and the role of different signaling pathways remain incompletely understood.
Purpose of the Study:
- To investigate whether changes in intestinal contractility during inflammation are specific to different agonists.
- To characterize the time-dependent alterations in both mechanical properties and agonist responses in an experimental colitis model.
Main Methods:
- Colitis was induced in rabbits using trinitrobenzenesulfonic acid.
- Intestinal strips were harvested at various time points (1, 2, 3, 5, 8 days) post-induction.
- Contractile responses to substance P (SP), motilin, acetylcholine (ACh), and potassium chloride (K+) were measured, along with passive tension and optimal stretch.
Main Results:
- Passive tension and optimal stretch increased, indicating structural changes in smooth muscle.
- Maximal active tension (Tmax) decreased significantly for all tested agonists, with varying time courses.
- Agonist potency (pEC50) showed distinct temporal changes, with ACh and SP responses affected differently than motilin.
Conclusions:
- Inflammation-induced changes in intestinal contractility are agonist-specific.
- The distinct temporal profiles of altered Tmax and pEC50 suggest that inflammation selectively impacts receptor-mediated signaling pathways.
- Generalized structural alterations in smooth muscle occur alongside specific functional deficits in agonist-receptor interactions.