Peristaltic Research Articles

Gut decontamination in the poisoned patient.

Poisoning management includes gastrointestinal decontamination strategies to decrease the burden of poison entering the body and change the expected severe toxicity expected to a less toxic, more favourable outcome. Common modalities are orogastric lavage, oral-activated charcoal and whole-bowel irrigation. Endoscopic retrieval and laparotomy are rare options reserved for severe ingestions and body packers. Although supporting data are generally of low quality, gastrointestinal decontamination is likely to improve patient outcome in many situations. Unfortunately, technical limitations and contraindications can explain their infrequent use. Orogastric lavage can be useful for early lethal ingestions, albeit with significant complications such as aspiration and perforation. Activated charcoal cannot adsorb every substance. Usual dosing is 1g/kg per dose. Whole-bowel irrigation is reserved for charged molecules or substances not adsorbed to activated charcoal but requires intact gut motility. Indications depend on several factors inherent to the ingestion (dose, time, poison) and patient's characteristics. During recent decades, studies of newer pharmaceuticals or modified-release formulations showed that significant amounts of poison, especially pharmacobezoars, persist in the gut hours postingestion, thus are amenable to gastrointestinal decontamination. Improved understanding of gut motility in volunteer studies and overdose showed clinically significant reduction in drug exposure with activated charcoal. The 1-h dogma for gastrointestinal decontamination, especially activated charcoal, is now obsolete. Clinicians must perform a risk assessment for each ingestion to determine the expected benefit at the time of decision-making, choosing the modality to achieve reduction in the toxicity burden while planning for complications or contraindications.

Optimizing bioconvective heat transfer with MHD Eyring–Powell nanofluids containing motile microorganisms with viscosity variability and porous media in ciliated microchannels

Purpose This paper aims to optimize bioconvective heat transfer for magnetohydrodynamics Eyring–Powell nanofluids containing motile microorganisms with variable viscosity and porous media in ciliated microchannels. Design/methodology/approach The flow problem is first modeled in the two-dimensional frame and then simplified under low Reynolds number and long wavelength approximations. The numerical method is used to examine the impact of thermal radiation, temperature-dependent viscosity, mixed convection, magnetic fields, Ohmic heating and porous media for velocity, temperature, concentration and motile microorganisms. Graphical results are presented to observe the impact of physical parameters on pressure rise, pressure gradient and streamlines. Findings It is observed that the temperature of nanofluid decreases with higher values of the viscosity parameter. It is absolutely in accordance with the physical expectation as the radiation parameter increases, the heat transfer rate at the boundary decreases. Nanoparticle concentration increases by increasing the values of bioconvection Rayleigh number. The density of motile microorganisms decreases when bioconvection Peclet number is increased. The velocity of the nanofluid decreases with higher value of Darcy number. With increase in the value of bioconvection parameter, the flow of nanofluid is increased. Originality/value The bioconvective peristaltic movement of magnetohydrodynamic nanofluid in ciliated media is proposed. The non-Newtonian behavior of the fluid is described by using an Eyring–Powell fluid model.

Dietary fiber source and stage of gestation impact water balance, fecal physicochemical properties, serum electrolytes, and markers of gut motility in sows

Dietary fiber source and stage of gestation impact water balance, fecal physicochemical properties, serum electrolytes, and markers of gut motility in sows

The C. elegans uv1 neuroendocrine cells provide mechanosensory feedback of vulval opening.

Neuroendocrine cells react to physical, chemical, and synaptic signals originating from tissues and the nervous system, releasing hormones that regulate various body functions beyond the synapse. Neuroendocrine cells are often embedded in complex tissues making direct tests of their activation mechanisms and signaling effects difficult to study. In the nematode worm C. elegans, four uterine-vulval (uv1) neuroendocrine cells sit above the vulval canal next to the egg-laying circuit, releasing tyramine and neuropeptides that feedback to inhibit egg laying. We have previously shown uv1 cells are mechanically deformed during egg laying, driving uv1 Ca2+ transients. However, whether egg-laying circuit activity, vulval opening, and/or egg release triggered uv1 Ca2+ activity was unclear. Here we show uv1 responds directly to mechanical activation. Optogenetic vulval muscle stimulation triggers uv1 Ca2+ activity following muscle contraction even in sterile animals. Direct mechanical prodding with a glass probe placed against the worm cuticle triggers robust uv1 Ca2+ activity similar to that seen during egg laying. Direct mechanical activation of uv1 cells does not require other cells in the egg-laying circuit, synaptic or peptidergic neurotransmission, or TRPV and Piezo channels. EGL-19 L-type Ca2+ channels, but not P/Q/N-type or Ryanodine Receptor Ca2+ channels, promote uv1 Ca2+ activity following mechanical activation. L-type channels also facilitate the coordinated activation of uv1 cells across the vulva, suggesting mechanical stimulation of one uv1 cells cross-activates the other. Our findings show how neuroendocrine cells like uv1 report on the mechanics of tissue deformation and muscle contraction, facilitating feedback to local circuits to coordinate behavior.Significance Statement Neuroendocrine cells respond to diverse physical and chemical signals from the body, releasing hormones that control reproduction, gut motility, and fight or flight responses. Neuroendocrine cells are often found embedded in complex tissues, complicating studies of how they are activated. Using the genetic and experimental accessibility of C. elegans, we find the uv1 neuroendocrine cells of the egg-laying motor behavior circuit respond directly to mechanical stimulation and vulval opening. We show that L-type voltage-gated Ca2+ channels facilitate uv1 mechanical activation and coordinate cell activation across the vulval opening. In contrast to other mechanically activated cells, uv1 activation does not require Piezo or TRPV channels. This work shows how neuroendocrine cells relay critical mechanosensory feedback to circuits that control reproduction.

Gut Neuropathies and Intestinal Motility Disorders.

The enteric nervous system plays a key role in the coordination of gastrointestinal motility together with sympathetic, parasympathetic, and extrinsic sensory pathways. In some cases, abnormalities in neural activity in these pathways contribute to disorders of gut motility. Where this is associated with damage or death of enteric neurons, usually detected by microscopy, this is considered a gut neuropathy. This review summarizes recent advances in the identification of neuropathies in a range of gastrointestinal motility disorders.

Effects of electroosmosis and entropy generation on a particulate-fluid suspension through peristaltic motion of Prandtl fluid: a numerical investigation

In thermodynamics, engineering, and environmental science, entropy generation are useful for comprehending complicated phenomena like heat transfer and fluid dynamics, analysing irreversibility, and optimising energy systems. Particulate-fluid flow with chemical reactions are employed in pharmaceutical manufacturing, catalytic converters, and combustion processes. This study provides insights into mass and thermal transmission analysis and influences of electroosmosis on flow of the Prandtl fluid in peristaltic micro-channel. The flow is also investigated considering the multiphase phenomenon influenced by chemical reaction. The flow problem modelling utilises lubrication theory with lengthy wavelengths and creeping flow assumptions. Furthermore, using Debye linearisation, the Poisson equation is simplified. The consequent structures for coupled ordinary differential equations have been handled by numerical solutions computed by using a highly efficient shooting technique with the help of NDSolve tool in Mathematica. It is concluded graphically that the profile of velocity declines with the increasing variation of porosity factor while enhances with the rise in Helmholtz-Smoluchowski velocity parameter. Thermal distribution increases with higher values of solid particle concentration and porous surface. It is evident that the concentration profile diminishes with the porosity coefficient but rises with the Helmholtz-Smoluchowski velocity factor.

Agonists of the opioid δ-receptor improve irritable bowel syndrome-like symptoms via the central nervous system.

Irritable bowel syndrome (IBS) is a common condition that is challenging to treat, and novel drugs are needed for this condition. Previously, a chronic vicarious social defeat stress (cVSDS) mouse model exhibits IBS-like symptoms. Also agonists of the opioid δ-receptor exert anti-stress effects in rodents with minimal adverse effects. Here, we evaluated the effects of δ-receptor agonists on the IBS-like symptoms in cVSDS mice. cVSDS mice (male C57BL/6J mice) were prepared following a 10-day exposure to witness of social defeat stress. Subsequently, intestinal peristaltic motility and abdominal hyperalgesia were evaluated using the charcoal meal test (CMT) and capsaicin-induced hyperalgesia test (CHT), respectively. Extracellular glutamate levels were measured using in vivo brain microdialysis. The drug was singly administrated 30 min before testing. In cVSDS mice, systemic (10 mg kg-1) and intracerebroventricular (30 nmol) administration of a δ-receptor agonist regulated intestinal peristalsis in the CMT and relieved abdominal pain in the CHT. Effects of systemic administration were blocked by intracerebroventricular injection of a δ-receptor inhibitor. Local infusion of the δ-receptor agonist (0.6 nmol) into the insular cortex improved cVSDS-induced intestinal hypermotility. The in vivo brain microdialysis study showed that re-exposure to VSDS elevated the extracellular glutamate levels in the IC, which was restored by the δ-receptor agonist. We propose that agonists of opioid δ-receptors are potential drugs for the radical treatment of IBS because they can ameliorate IBS-like symptoms via the CNS, specifically the insular cortex.

Pyloric web : Management of a neglected case of Gastric Outlet Obstruction

Pyloric atresia is an extremely rare cause of gastric outlet obstruction, constituting approximately 1% of all gastrointestinal atresias and occurring in about 1 in 100,000 live births. It is equally prevalent in males and females and may exhibit autosomal recessive inheritance. Clinically, it presents during infancy with non-bilious vomiting, abdominal distension, and failure to thrive. Type 1 pyloric atresia, characterized by a pyloric membrane with an opening, is exceptionally rare and may present later in childhood. We reported the case of a 5-year-old male with the history of recurrent non-bilious vomiting since the age of one year, which worsened over the preceding four months. Examination revealed visible peristalsis and upper abdominal fullness. Radiological findings suggested gastric outlet obstruction, and exploratory laparotomy confirmed Type 1 pyloric atresia. Surgical management involved excision of the pyloric web and Heineke-Mikulicz pyloroplasty. The child had an uneventful recovery and demonstrated significant improvement in weight and nutritional status at a 6-month follow-up. The diagnosis of pyloric atresia is challenging due to its rarity and similarity to other conditions like duodenal atresia or hypertrophic pyloric stenosis. Early diagnosis through clinical suspicion, radiological evaluation, and definitive surgical intervention is crucial to prevent complications such as aspiration pneumonia and metabolic imbalances. This case highlights the importance of considering pyloric atresia in children with recurrent vomiting and failure to thrive, even beyond infancy, and emphasizes the significance of prompt surgical management for favorable outcomes.

A Worm-like Soft Robot Based on Adhesion-Controlled Electrohydraulic Actuators.

Worms are organisms characterized by simple structures, low energy consumption, and stable movement. Inspired by these characteristics, worm-like soft robots demonstrate exceptional adaptability to unstructured environments, attracting considerable interest in the field of biomimetic engineering. The primary challenge currently involves improving the motion performance of worm-like robots from the perspectives of actuation and anchoring. In this study, a single segment worm-like soft robot driven by electrohydraulic actuators is proposed. The robot consists of a soft actuation module and two symmetrical anchoring modules. The actuation modules enable multi-degree-of-freedom motion of the robot using symmetric dual-electrode electrohydraulic actuators, while the anchoring modules provide active friction control through bistable electrohydraulic actuators. A hierarchical microstructure design is used for the biomimetic adhesive surface, enabling rapid, reversible, and stable attachment to and detachment from different surfaces, thereby improving the robot's surface anchoring performance. Experimental results show that the designed robot can perform peristaltic and bending motions similar to a worm. It achieves rapid bidirectional propulsion on both dry and wet surfaces, with a maximum speed of 10.36 mm/s (over 6 velocity/length ratio (min-1)).

Effect of Aqueous Extract of Glycyrrhiza glabra on rabbit ileum motility in comparison with Acetylcholine, Atropine and Ondansetron

Objectives: Gastrointestinal disorders such as irritable bowel syndrome can affect the quality of life and increase the risk of psychological problems such as depression. Drugs such as hyoscyamine and metoclopramide and 5-HT3 receptor antagonists such as Alosteron are used nowadays for symptomatic management, but their use is associated with adverse effects leading to decreased patient compliance. Nowadays, natural plant-based medicine is preferred by people due to its fewer adverse effects; therefore, the current study was planned to evaluate the effect of Glycyrrhiza glabra on the intestinal smooth muscle of rabbits. Our study aims to define the mechanism of action of G. glabra in promoting or inhibiting gut motility. Materials and Methods: An experimental in vitro study was conducted in the Pharmacology Department of Services Institute of Medical Sciences Lahore in January 2023. Rabbit ileal tissue was used. PowerLab (ADInstruments) was used to record the contractions of ileal smooth muscles. After mounting, the tissue was given to rest for 30 min, after which baseline contractions were recorded. Then, 0.8 mL of acetylcholine (10−5) was added, and contractions were recorded for 30 s. Freshly prepared Tyrode’s solution was used to rinse the tissue three and then given rest for 3 min. Then, ileal tissue was treated with G. glabra 5%, 15% and 20% and their effect was recorded. Acetylcholine served as a positive control, and the action of G. glabra 5%, 15% and 20% solution was compared with it. After that, G. glabra was used in the presence of drugs that inhibit intestinal motility, atropine and ondansetron 0.0036 µM and 0.036 µM, respectively. Results: Results showed that G. glabra 5%, 15% and 20% increased intestinal motility significantly (P < 0.0001) in comparison with acetylcholine. However, when G. glabra was used in the presence of antagonists, atropine and ondansetron, then, it reduced intestinal motility significantly (P < 0.0001). Conclusion: Aqueous extract of G. glabra has a dual effect on gut motility that is a direct muscarinic receptor agonist and indirect modulator of enteric vagus nerve terminal through serotonin 5-HT3 receptors.

Intraoperative evaluation of the intestinal wall viability

An analysis of data from national and foreign literature was carried out in terms of intraoperative determination of the intestinal viability in cases of developing the diseases in the abdominal cavity organs, associated with impaired intestinal blood supply. The basis of this work is the analysis of the modern literature on the methods of intraoperative evaluation of mesenteric ischemia. Impaired mesenteric blood supply is often the consequence of a number of reasons of developing critical conditions (mesenteric thrombosis, acute adhesive intestinal obstruction, incarcerated hernia etc.), also representing a high risk factor for lethal outcomes. Special attention is paid to the occlusion-related pathogenetic mechanism of developing mesenteric ischemia, which is accompanied by rapid development of irreversible morphological changes in the tissues and by significant disorders in the homeostasis systems of the organism. The generally available method for visual evaluation of the intestine viability is not always valid in terms of determining the degree of intensity of the ischemic changes in the intestinal wall. The algorithm of determining the intestine viability includes the determination of the intestine color, the peristaltic motions, the pulsation and the blood filling of mesenteric vessels with dynamic evaluation of these signs after the injecting the local anesthetic drug solution into the mesenterium and after “warming” the intestine with towels soaked in warm sodium chloride solution. In the current surgical conditions, a more precise method is required for intraoperative determination of the tissue viability. For the purpose of the objective evaluation of the intestinal blood supply, the recommendations include using intraoperative ultrasonic and laser Doppler flowmetry, as well as the regional transillumination angiotensometry of the intramural vessels in the small intestine. At the same time, a number of optical spectroscopy and visualization methods show high sensitivity to changes in blood microcirculation without using exogenous contrasting, which can also be successfully used when evaluating the intestinal circulation. According to data from modern literature, there is still controversy on the efficiency of various methods for intraoperative evaluation of disorders of the regional blood microcirculation and the intestine viability, which justifies the conduct of further research works.

Impact of Permeable Lining of the Wall on the Peristaltic Flow of Rabinowitsch Fluid in a Vertical Channel

Rabinowitsch fluid model is a well-established model for studying the non-Newtonian nature of the fluid This study is carried out to analyze the Rabinowitsch fluid through flexible and symmetric vertical channel with suction and injection under peristaltic motion. Considering long wavelength and low Reynolds number assumptions,. The present work is the mathematical investigation of permeable lining of the wall on the peristaltic flow of Rabinowitsch fluid in vertical channel with suction and injection . Pressure rise and the variation of various influencing parameters of the flow are studied graphically Keywords: peristalsis,vertical channel, Rabinowitsch fluid ,porous thickness of wall, permeable wall,

Numerical study of entropy production and EMHD effects in a peristaltic motion of Prandtl fluid with solid particles and porous medium

Particulate-fluid flow involving chemical reactions plays a crucial role in pharmaceutical manufacturing, catalytic converters, and combustion processes. This research focuses on the analysis of mass and thermal transfer, highlighting the influence of electroosmosis and magnetic forces on the flow of Prandtl fluid through a peristaltic porous micro-channel. In addition, the multiphase flow attitude, affected by chemical reactions, is extensively examined. The flow model is formulated by utilizing the lubrication theory estimation, integrating lengthy-wavelength and creeping flow approximation to simplify the considered problem. To further simplify the problem, Debye linearization is used, resulting in a set of two ordinary differential equations. The outcomes indicate that velocity drops with rising magnetic field, while it enhances with the Helmholtz-Smoluchowski velocity coefficient. Furthermore, thermal distribution increases with greater concentrations of solid fragments and greater magnetic field. These findings provide valuable insights into optimizing mass and thermal conveyance in peristaltic problems, with potential appliances spanning numerous industrial and biomedical areas.

Integration of artificial neural network computing for radially magnetized bioconvection peristaltic movement of Reiner-Philippoff nanofluid with porous medium

Integration of artificial neural network computing for radially magnetized bioconvection peristaltic movement of Reiner-Philippoff nanofluid with porous medium

Spatiotemporal dynamics of the developing zebrafish enteric nervous system at the whole-organ level.

Neural crest cells give rise to the neurons of the enteric nervous system (ENS) that innervate the gastrointestinal (GI) tract to regulate gut motility. The immense size and distinct subregions of the gut present a challenge to understanding the spatial organization and sequential differentiation of different neuronal subtypes. Here, we profile enteric neurons (ENs) and progenitors at single-cell resolution during zebrafish embryonic and larval development to provide a near-complete picture of transcriptional changes that accompany the emergence of ENS neurons throughout the GI tract. Multiplex spatial RNA transcript analysis identifies the temporal order and distinct localization patterns of neuronal subtypes along the length of the gut. Finally, we show that functional perturbation of select transcription factors Ebf1a, Gata3, and Satb2 alters the cell fate choice, respectively, of inhibitory, excitatory, and serotonergic neuronal subtypes in the developing ENS.

Human norovirus disturbs intestinal motility and transit time through its capsid proteins.

Human norovirus (HuNoV) accounts for over 700 million cases of gastroenteritis annually. Episodes of HuNoV disease are characterized by vomiting and diarrhea as the two most prominent symptoms. Despite its prevalence, our understanding of the pathophysiological mechanisms triggered upon HuNoV infection is limited, mainly due to a lack of suitable animal models. Our aim was to use the recent HuNoV zebrafish larvae model to study the effect of HuNoV infection on intestinal motility and investigate whether one viral protein could act as an enterotoxin, as seen with rotavirus. We studied whether HuNoV infection affects the contraction frequency of the intestinal bulb and the posterior intestine as well as the transit time. Infection of larvae, following injection of a HuNoV GII.4-containing stool sample in the yolk, resulted in an increased contraction frequency in the intestinal bulb. A comparable effect was observed in serotonin-treated larvae, corresponding to the natural function of serotonin. The higher replication efficacy of HuNoV GII.4 likely explains why they have a more marked effect on gut motility, when compared to other genotypes. Additionally, transit time of fluorescent food was prolonged in HuNoV GII.4 infected larvae, suggesting a loss of coordination in bowel movements upon infection. To identify the proteins responsible for the effect, individual HuNoV non-structural proteins and virus-like particles (VLPs) were injected intraperitoneally (ip). VLPs carrying VP1/VP2, but not those with only VP1, induced increased contraction frequencies in the intestinal bulb in a dose-dependent manner. In conclusion, our findings suggest that the viral capsid and potentially the minor capsid protein VP2 play a crucial role in the aetiology of symptoms associated with HuNoV, potentially acting as a viral enterotoxin. This work contributes to the understanding of the pathophysiological mechanisms in HuNoV-induced disease and further attests zebrafish as a valuable HuNoV disease model.

Organ-specific sympathetic innervation defines visceral functions.

The autonomic nervous system orchestrates thefunctions of the brain and body through the sympathetic and parasympathetic pathways1. However, our understanding of the autonomic system, especially the sympathetic system, at the cellular and molecular levels is severely limited. Here we show topological representations of individual visceral organs in the major abdominal sympathetic ganglion complex. Using multi-modal transcriptomic analyses, we identified molecularly distinct sympathetic populations in the coeliac-superior mesenteric ganglia (CG-SMG). Of note, individual CG-SMG populations exhibit selective and mutually exclusive axonal projections to visceral organs, targeting either the gastrointestinal tract or secretory areas including the pancreas and bile tract. This combinatorial innervation pattern suggests functional segregation between different CG-SMG populations. Indeed, our neural perturbation experiments demonstrated that one class of neurons regulates gastrointestinal transit, and another class of neurons controls digestion and glucagon secretion independent of gut motility. These results reveal the molecularly diverse sympathetic system and suggest modular regulation of visceral organ functions by sympathetic populations.

Whole Gut Motility Patterns in Patients with Chronic Nausea and Vomiting.

Background/Objectives: Chronic nausea and vomiting (N/V) disorders are common in clinical practice. Our primary aim was to compare total and segmental gastrointestinal transit times as well as gastric contraction patterns in patients with chronic N/V syndrome to those of healthy volunteers (HVs). In the patient group, our secondary aim was to explore how symptoms and motility patterns were affected by a serotonin HT4 receptor agonist (Prucalopride). Methods: Patients with chronic N/V syndrome and HVs underwent baseline assessment of regional gastrointestinal (GI) motility/transit using the Motilis 3D-Transit system. Patients were then treated with Prucalopride 2 mg daily for 28 days, with the 3D-transit examination repeated within 10-20 days after treatment onset. Two self-administered questionnaires (the Gastrointestinal Symptom Rating Scale [GSRS] and Gastroparesis Cardinal Symptom Index [GCSI]) were used to assess patients' symptoms. Results: A total of 19 patients (13 F; median age 25 years (IQR 22-39) and 55 HVs (25 F; median age 28 (24-35) were included. At baseline, no differences in regional GI transit times were found between groups. However, patients had a significantly lower gastric contraction amplitude than HVs (9 mmHg (IQR 8-11) vs. 12 (10-15: p < 0.001). In response to Prucalopride treatment, gastric emptying time was reduced from a median of 3.1 h to 1.6 h (p < 0.005). Further, the GCSI was significantly reduced from GCSI 3.0 (IQR 2.3-3.7) at baseline to GCSI 1.9 (IQR 1.3-3.2) with Prucalopride. Conclusions: Patients with chronic N/V syndrome have significantly lower gastric contraction amplitude than HVs and may symptomatically benefit from prokinetics. They do not, however, have evidence of panenteric dysmotility.

Impact of Physical Activity on Digestive System Diseases

ABSTRACT Introduction: Digestive system diseases, including IBD, and GERD, are prevalent health concerns worldwide. Physical activity, widely acknowledged for its health benefits, has emerged as a promising area of research for its potential in mitigating symptoms and influencing risk factors associated with digestive system diseases. This study aims to critically assess existing evidence on the role of physical activity in the prevention, symptom management, and progression of prevalent digestive disorders. Materials and Methods: A systematic review of pertinent studies was conducted through comprehensive searches in databases including PubMed, NCBI and Google Scholar. The data were sourced from clinical and experimental studies, evaluated for methodological rigor, participant characteristics, and therapeutic outcomes. State of knowledge: The analysis demonstrated that physical activity can exert beneficial effects on digestive health through mechanisms such as enhanced gut motility, reduced inflammation, and increased microbiota diversity. Moderate-intensity aerobic exercise was associated with reduced risk and symptom improvement in patients with IBS and IBD, while high-intensity exercise showed variable effects, with potential symptom exacerbation in certain cases. Additionally, exercise correlated with a lower incidence of GERD, likely due to benefits in weight management. Despite these positive associations, inconsistencies in study design and exercise protocols underscore the need for standardized guidelines on physical activity tailored to specific digestive conditions. Conclusions: Physical activity appears to play a beneficial role in managing and potentially preventing certain digestive system diseases. While moderate exercise shows promise in symptom alleviation and risk reduction, further research is necessary to establish clear, condition-specific exercise recommendations.

Integrated responses of the SIP syncytium generate a major motility pattern in the colon.

The peristaltic reflex has been a central concept in gastrointestinal motility; however, evidence was published recently suggesting that post-stimulus responses that follow inhibitory neural responses provide the main propulsive force in colonic motility. This new concept was based on experiments on proximal colon where enteric inhibitory neural inputs are mainly nitrergic. However, the nature of inhibitory neural inputs changes from proximal to distal colon where purinergic inhibitory regulation dominates. In spite of the transition from nitrergic to purinergic regulation, post-stimulus responses and propulsive contractions were both blocked by antagonists of a conductance (ANO1) exclusive to interstitial cells of Cajal (ICC). How purinergic neurotransmission, transduced by PDGFRα+ cells, can influence ANO1 in ICC is unknown. We compared neural responses in proximal and distal colon. Post-stimulus responses were blocked by inhibition of nitrergic neurotransmission in proximal colon, but P2Y1 receptor antagonists were more effective in distal colon. Ca2+ entry through voltage-dependent channels (CaV3) enhances Ca2+ release in ICC. Thus, we reasoned that hyperpolarization caused by purinergic responses in PDGFRα+ cells, which are electrically coupled to ICC, might decrease inactivation of CaV3 channels and activate Ca2+ entry into ICC via anode-break upon cessation of inhibitory responses. Post-stimulus responses in distal colon were blocked by MRS2500 (P2Y1 receptor antagonist), apamin (SK channel antagonist) and NNC55-0396 (CaV3 antagonist). These compounds also blocked propagating contractions in mid and distal colon. These data provide the first clear demonstration that integration of functions in the smooth muscle-ICC-PDGFRα+ cell (SIP) syncytium generates a major motility behaviour. KEY POINTS: Propagating propulsive contractions initiated by the enteric nervous system are a major motility behaviour in the colon. A major component of contractions, necessary for propulsive contractions, occurs at cessation of enteric inhibitory neurotransmission (post-stimulus response) and is generated by interstitial cells of Cajal (ICC), which are electrically coupled to smooth muscle cells. The nature of enteric inhibitory neurotransmission shifts from proximal colon, where it is predominantly due to nitric oxide, to distal colon, where it is predominantly due to purine neurotransmitters. Different cells transduce nitric oxide and purines in the colon. ICC transduce nitric oxide, but another type of interstitial cell, PDGFRα+ cells, transduces input from purinergic neurons. However, the post-stimulus responses in proximal and distal colon are still generated in ICC. This paper explores how integrated behaviours of ICC, PDGFRα+ cells and smooth muscle cells accomplish propulsive motility in the colon.