Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.

Relationship between genotypes and clinical manifestation, pathology, and cccDNA in Chinese children with hepatitis B virus-associated glomerulonephritis

Background:Hepatitis B virus-associated glomerulonephritis(HBV-GN)is one of the extrahepatic manifestations after HBV infection,which would cause great clinical harm to people.The present study was undertaken to investigate the HBV-GN genotypes and its clinical relevance in Chinese children.Methods:A total of 41 HBV-infected children diagnosed with HBV-GN were enrolled in the study.All patients underwent liver and kidney biopsy.The genotypes and cccDNA were detected in their serum samples to analyze the relationship between HBV genotypes and clinical characteristics,cccDNA,and pathology.Results:Among the 41 children with HBV-GN,29(70.7%)had genotype C,10(24.4%)had genotype B,2(4.9%)had genotype B/C,and none of them had genotype non-B/C.Most children had genotypes B or C;moreover,the genotype C was the most frequent one.The incidence of hematuria and albuminuria,reduction in complement C3,increase in serum alanine aminotransferase levels and renal insufficiency in the children with genotype C were signifi cantly higher than those in the children with genotype B(P<0.05);however,there was no statistically significant difference in hypertension and hepatomegaly(P>0.05).The frequency of HBV cccDNA positive in the genotype C group was significantly higher than that in the genotype B group(72.4%vs.30.0%,P<0.05).No difference was observed in hepatic inflammation grades and stages of fibrosis between the two groups(P>0.05).Conclusion:Genotype C was the most frequent genotype in the described group of patients with HBV-GN,and the liver and kidney damage indicators were more likely to occur in patients with genotype C.