Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis

Abstract

BACKGROUND The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC. AIM To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model. METHODS Male rats ( n = 8/each group) were randomly divided into a control (CG), a UC group (EG1), a UC + thrombin derived polypeptide 508 trifluoroacetic acid (TP508TFA; an NOS agonist) group (EG2), and a UC + NG-monomethyl-L-arginine monoacetate (L-NMMA; an NOS inhibitor) group (EG3). UC was induced by administering 5.5% DSS in drinking water without any other treatment (EG1), while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA, respectively. The disease activity index (DAI) and histological assessment were recorded for each group, whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining, Western blot, and enzyme linked immunosorbent assay, respectively. In addition, the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system. RESULTS The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1, EG2, and EG3 than in the CG group. Compared with the EG1, the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated, respectively. Thus, during UC, regulation of the expression of NOS within the MP improved the intestinal motility, thereby favoring the recovery of intestinal functions. CONCLUSION In UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These resu...

A novel beneficial role of humanin on intestinal apoptosis and dysmotility in a rat model of ischemia reperfusion injury

“…According to reports, inflammatory mediators and their metabolites may alter neuromotor function, which would alter motility [ 3 , 22 , 42 , 59 ]. These inflammatory processes may also impact other organs in addition to the intestine [ 45 ].…”

“…Notably, some gastrointestinal motor dysfunctions have been attributed to alter NO generation or release [ 21 , 30 ]. Selective iNOS inhibition has been proposed as a therapy method for this potentially fatal illness, and it has been postulated that a toxic megacolon in individuals with ulcerative colitis may be generated by an excess of NO produced by iNOS in the colonic smooth muscles [ 45 ]. Colonic hypomotility seen in induced chronic pancreatitis has also been reported to be caused by elevated iNOS in the myenteric plexus, thus, proving the contribution of NOS in the pathogenesis of colonic dysmotility [ 15 ].…”

“…It is understood that NO keeps a balance between vasoconstriction and vasodilatation [ 37 ]. The modulation of smooth muscle contractions by NO via nonadrenergic noncholinergic neurons is essential [ 45 ]. Therefore, changes in the basal level of NO or I/R-induced NO generation may affect intestinal motility.…”

Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level

“…In this study, we predicted eight key active compounds in WDG that may be responsible for its therapeutic effects. Previous studies have reported that beta-sitosterol ( Kasirzadeh et al, 2021 ), stearic acid ( Sobocinska et al, 2022 ), linoleic acid ( Zhang et al, 2021 ), and lauric acid ( Li et al, 2022 ) exert pharmacological effects on the regulation of intestinal inflammation and the intestinal gut function, both of which are consistent with the mechanism of GMD. However, there remains a lack of reports on the effect of 4-tetradecenoic acid, 5Z-tetradecenoic acid, myristelaidic acid, and 11-dodecenoic acid on gastrointestinal disorders, prompting us to focus on these drugs with potential functions in GMD in future studies.…”