Numerical simulations of effects of multiple neurotransmission on intestinal propulsion of a non-deformable bolus

Electrophysiological mechanisms of co-transmission by serotonin (5-HT) and acetylcholine (ACh), co-expression of receptor types 5-HT type 3 and 4, nicotinic cholinerginc (nACh) and muscarinic cholinergic (mACh), and effects of selective and non-selective 5-HT3 and 5-HT4 receptor agonists/antagonists, on intestinal propulsion of a solid non-deformable bolus were studied numerically. Results indicated that the propagation of the wave of excitation in the presence of 5-HT3 receptor antagonists was supported by co-release of ACh. Co-stimulation of 5-HT3, nACh and mACh receptors significantly impairs propulsive activity of the gut. In an ACh-free environment, Lotronex increased the transit time of the bolus along a segment of the gut. In the presence of ACh, Lotronex produced intensive tonic-type contractions in the longitudinal and circular smooth muscle layers and eliminated propulsive activity. Zelnorm preserved the reciprocal electromechanical relationships between the longitudinal and circular smooth muscle layers. The drug changed the normal mixing pattern of activity to an expulsive type. Treatment of the gut with selective 5HT4 receptor antagonists increased the transit time by disrupting the migrating myoelectrical complex. Cisapride increased the excitability of the myenteric nervous plexus and increased the frequency of slow waves. In the presence of Cisapride smooth muscle syncytia responded with the generation of tonic contractions, resulting in a “squeezing” type of bolus movement. Comparison of the theoretical results to in vivo and in vitro experimental data indicated satisfactory qualitative and quantitative agreement.