prucalopride and Inflammation

Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder.. This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition.

Topics: Anesthesia, Epidural; Animals; Benzofurans; Chewing Gum; Cholinergic Agents; Contrast Media; Cyclooxygenase Inhibitors; Diatrizoate Meglumine; Digestive System Surgical Procedures; Enhanced Recovery After Surgery; Enteral Nutrition; Enteric Nervous System; Fluid Therapy; Gastrointestinal Agents; Gastrointestinal Motility; Ghrelin; Humans; Ileus; Inflammation; Intestinal Pseudo-Obstruction; Intubation, Gastrointestinal; Laparoscopy; Mast Cells; Piperidines; Postoperative Complications; Serotonin 5-HT4 Receptor Agonists; Sympathetic Nervous System; Sympatholytics

Vagus nerve stimulation (VNS), most likely via enteric neurons, prevents postoperative ileus (POI) by reducing activation of alpha7 nicotinic receptor (α7nAChR) positive. EFS reduced the ATP-induced Ca. Enteric neurons dampen mMφ activation, an effect mimicked by prucalopride. Preoperative, but not postoperative treatment with prucalopride prevents intestinal inflammation and shortens POI in both mice and human, indicating that preoperative administration of 5-HT4R agonists should be further evaluated as a treatment of POI.. NCT02425774.

Topics: Adult; alpha7 Nicotinic Acetylcholine Receptor; Animals; Benzofurans; Disease Models, Animal; Female; Gastrointestinal Motility; Humans; Ileus; Inflammation; Intestine, Small; Macrophages; Male; Mice; Muscle, Smooth; Pancreaticoduodenectomy; Pilot Projects; Postoperative Complications; Serotonin 5-HT4 Receptor Agonists; Treatment Outcome

Evidence suggests constipation precedes motor dysfunction and is the most common gastrointestinal symptom in Parkinson's disease (PD). 5-HT4 receptor (5-HT4R) agonist prucalopride has been approved to treat chronic constipation. Here, we reported intraperitoneal injection of prucalopride for 7 days increased dopamine and decreased dopamine turnover. Prucalopride administration improved motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mouse models. Prucalopride treatment also ameliorated intestinal barrier impairment and increased IL-6 release in PD model mice. However, prucalopride treatment exerted no impact on JAK2/STAT3 pathway, suggesting that prucalopride may stimulate IL-6 via JAK2/STAT3-independent pathway. In conclusion, prucalopride exerted beneficial effects in MPTP-induced Parkinson's disease mice by attenuating the loss of dopamine, improving motor dysfunction and intestinal barrier.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Benzofurans; Body Weight; Disease Models, Animal; Dopamine; Eating; Inflammation; Interleukin-6; Intestinal Mucosa; Janus Kinase 2; Male; Mice; Mice, Inbred C57BL; Motor Skills; MPTP Poisoning; Neostriatum; Parkinson Disease; Parkinson Disease, Secondary; STAT3 Transcription Factor

Topics: Benzofurans; Cholinergic Agents; Humans; Ileus; Inflammation; Neurons; Postoperative Complications; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists

Topics: Benzofurans; Enteric Nervous System; Inflammation; Neurons; Neuroprotective Agents; Oxidative Stress; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists