scholarly journals Positive Correlation between nNOS and Stress-Activated Bowel Motility Is Confirmed by In Vivo HiBiT System

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1028
Author(s):  
Jeong Pil Han ◽  
Jeong Hyeon Lee ◽  
Geon Seong Lee ◽  
Ok Jae Koo ◽  
Su Cheong Yeom

Neuronal nitric oxide synthase (nNOS) has various roles as a neurotransmitter. However, studies to date have produced insufficient data to fully support the correlation between nNOS and bowel motility. This study aimed to investigate the correlation between nNOS expression and gastrointestinal (GI) tract motility using a stress-induced neonatal maternal separation (NMS) mouse model. In this study, we generated a genetically modified mouse with the HiBiT sequence knock-in into the nNOS gene using CRISPR/Cas9 for analyzing accurate nNOS expression. nNOS expression was measured in the stomach, small intestine, large intestine, adrenal gland, and hypothalamus tissues after establishing the NMS model. The NMS model exhibited a significant increase in nNOS expression in large intestine, adrenal gland, and hypothalamus. Moreover, a significant positive correlation was observed between whole gastrointestinal transit time and the expression level of nNOS. We reasoned that NMS induced chronic stress and consequent nNOS activation in the hypothalamic-pituitary-adrenal (HPA) axis, and led to an excessive increase in intestinal motility in the lower GI tract. These results demonstrated that HiBiT is a sensitive and valuable tool for analyzing in vivo gene activation, and nNOS could be a biomarker of the HPA axis-linked lower intestinal tract dysfunction.

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
E. Moura ◽  
C. Esteves-Pinto ◽  
M.P. Serrão ◽  
I. Azevedo ◽  
M. Vieira-Coelho

Introduction:The efficacy of antidepressants has been linked in part to their ability to reduce activity of the hypothalamic-pituitary-adrenal (HPA) axis; however, the mechanism by which antidepressants regulate the HPA axis is largely unknown. Recent research has demonstrated that endocannabinoids can regulate the HPA axis and exhibit antidepressant potential.Aim:The purpose of this study was therefore to evaluate the effect of chronic administration of delta-9-tetrahydrocannabinol (delta9-THC) on the adrenal gland of mice.Methods:Delta9-THC (10 mg/kg, 1 THC:1 chremophor:18 saline) or vehicle (CT, 1 chremophor:18 saline) was administered i.p. for 10 days to C57Bl6 mice aged 15 weeks. At the end of the study rats were placed in metabolic cages. Noradrenaline (NA) and adrenaline (AD) levels in samples and tissues were evaluated by HPLC-ED. Statistical analysis was done by ANOVA followed by Student's t test. Results are presented as mean±SEM.Results:Treatment with delta9-THC did not produce changes in mice weight (CT: 25±1; delta9-THC: 24±1 g, n=5-6) but produced a significant reduction in adrenal gland weight (CT: 1.4±0.2; delta9-THC: 0.6±0.1* mg, n=5-6, *P˂0.01). However, treatment with delta9-THC did not produce significant changes in NA and AD adrenal content (NA: 7.5±2.1, 5.3±0.6; AD: 14.1±1.1, 11.1±2.1 nmol, CT and delta9-THC respectively, n=5-6) or in NA and AD urine levels (NA: 0.88±0.06, 1.18±0.17; AD: 0.64±0.07, 0.81±0.09 nmol/24h, CT and delta9-THC respectively, n=5-6).Conclusion:Chronic treatment with delta9-THC reduces adrenal gland weight in mice. These results suggest that endocannabinoids may act directly at the adrenal gland to regulate the HPA axis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ling Li ◽  
Mohamad I. Itani ◽  
Kevan J. Salimian ◽  
Yue Li ◽  
Olaya Brewer Gutierrez ◽  
...  

AbstractGastrointestinal (GI) strictures are difficult to treat in a variety of disease processes. Currently, there are no Food and Drug Administration (FDA) approved drugs for fibrosis in the GI tract. One of the limitations to developing anti-fibrotic drugs has been the lack of a reproducible, relatively inexpensive, large animal model of fibrosis-driven luminal stricture. This study aimed to evaluate the feasibility of creating a model of luminal GI tract strictures. Argon plasma coagulation (APC) was applied circumferentially in porcine esophagi in vivo. Follow-up endoscopy (EGD) was performed at day 14 after the APC procedure. We noted high grade, benign esophageal strictures (n = 8). All 8 strictures resembled luminal GI fibrotic strictures in humans. These strictures were characterized, and then successfully dilated. A repeat EGD was performed at day 28 after the APC procedure and found evidence of recurrent, high grade, fibrotic, strictures at all 8 locations in all pigs. Pigs were sacrificed and gross and histologic analyses performed. Histologic examination showed extensive fibrosis, with significant collagen deposition in the lamina propria and submucosa, as well as extensive inflammatory infiltrates within the strictures. In conclusion, we report a porcine model of luminal GI fibrotic stricture that has the potential to assist with developing novel anti-fibrotic therapies as well as endoscopic techniques to address recurring fibrotic strictures in humans.


Nature ◽  
1969 ◽  
Vol 221 (5180) ◽  
pp. 572-573 ◽  
Author(s):  
MARGARETHE HOLZBAUER ◽  
HELEN M. NEWPORT ◽  
MARION K. BIRMINGHAM ◽  
HELLI TRAIKOV
Keyword(s):  

2000 ◽  
Author(s):  
David C. O. Pickard ◽  
Gavin M. Briggs ◽  
Christobel Saunders ◽  
Sunil Lakhani ◽  
Paul M. Ripley ◽  
...  

2001 ◽  
Vol 67 (7) ◽  
pp. 3071-3076 ◽  
Author(s):  
Ren� L. van Winsen ◽  
Bert A. P. Urlings ◽  
Len J. A. Lipman ◽  
Jos M. A. Snijders ◽  
David Keuzenkamp ◽  
...  

ABSTRACT An in vivo experiment was performed with pigs to study the inhibitory effect of fermented feed on the bacterial population of the gastrointestinal tract. Results demonstrated a significant positive correlation between pH and lactobacilli in the stomach contents of pigs in dry feed as well as in the stomach contents of pigs fed fermented feed. Furthermore, a significant positive correlation between the pH and the numbers of bacteria in the familyEnterobacteriaceae in the contents of the stomach of pigs fed dry feed was found. In the stomach contents of pigs fed fermented feed, a significant negative correlation was found between the concentration of the undissociated form of lactic acid and the numbers of Enterobacteriaceae. The numbers ofEnterobacteriaceae in the contents of the stomach, ileum, cecum, colon, and rectum of pigs fed fermented feed were significantly lower compared with the contents of the stomach, ileum, caecum, colon, and rectum of pigs fed dry feed. The numbers of total lactobacilli were significantly higher in the stomach contents of pigs fed fermented feed and in the ileum contents of one pig group fed fermented feed compared with the contents of pigs fed dry feed. However, the influence of lactobacilli on numbers of Enterobacteriaceae could not be demonstrated. It was concluded that fermented feed influences the bacterial ecology of the gastrointestinal tract and reduces the levels of Enterobacteriaceae in the different parts of the gastrointestinal tract.


2011 ◽  
Vol 46 (3) ◽  
pp. 227-232 ◽  
Author(s):  
Rebecca J Gorrigan ◽  
Leonardo Guasti ◽  
Peter King ◽  
Adrian J Clark ◽  
Li F Chan

The melanocortin-2-receptor (MC2R)/MC2R accessory protein (MRAP) complex is critical to the production of glucocorticoids from the adrenal cortex. Inactivating mutations in either MC2R or MRAP result in the clinical condition familial glucocorticoid deficiency. The localisation of MC2R together with MRAP within the adrenal gland has not previously been reported. Furthermore, MRAP2, a paralogue of MRAP, has been shown in vitro to have a similar function to MRAP, facilitating MC2R trafficking and responsiveness to ACTH. Despite similar MC2R accessory functions, in vivo, patients with inactivating mutations of MRAP fail to be rescued by a functioning MRAP2 gene, suggesting differences in adrenal expression, localisation and/or function between the two MRAPs. In this study on the rat adrenal gland, we demonstrate that while MRAP and MC2R are highly expressed in the zona fasciculata, MRAP2 is expressed throughout the adrenal cortex in low quantities. In the developing adrenal gland, both MRAP and MRAP2 are equally well expressed. The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex. Interestingly, expression of MC2R and MRAP in the undifferentiated zone would support the notion that ACTH may play an important role in adrenal cell differentiation and maintenance.


1969 ◽  
Vol 43 (1) ◽  
pp. 135-136 ◽  
Author(s):  
N. DESHPANDE ◽  
V. JENSEN ◽  
R. D. BULBROOK ◽  
T. W. DOOUSS
Keyword(s):  

1997 ◽  
Vol 273 (1) ◽  
pp. G184-G190 ◽  
Author(s):  
M. Saghir ◽  
J. Werner ◽  
M. Laposata

Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, are in use as fatty acid supplements, but they also have been implicated as toxic mediators of ethanol ingestion. We hypothesized that hydrolysis of orally ingested FAEE occurs in the gastrointestinal (GI) tract and in the blood to explain their apparent lack of toxicity. To study the in vivo inactivation of FAEE by hydrolysis to free fatty acids and ethanol, we assessed the hydrolysis of FAEE administered as an oil directly into the rat stomach and when injected within the core of low-density lipoprotein particles into the circulation of rats. Our studies demonstrate that FAEE are rapidly degraded to free fatty acids and ethanol in the GI tract at the level of the duodenum with limited hydrolysis in the stomach. In addition, FAEE are rapidly degraded in the circulation, with a half-life of only 58 s. Thus the degradation of FAEE in the GI tract and in the blood provides an explanation for the apparent lack of toxicity of orally ingested FAEE.


2009 ◽  
pp. 757-761
Author(s):  
CF Sharpley ◽  
KG Kauter ◽  
JR McFarlane

Cortisol is secreted by the central hypothalamo-pituitary-adrenal axis and affects many target organs and tissues, particularly in response to stressor demands and infection. Recent data reporting cortisol synthesis in hair follicles have shown the existence of a parallel “peripheral” HPA-axis. However, although there is evidence from in vitro studies and single-observation comparisons between groups that cortisol from hair follicles reflects endocrine changes associated with stressor demands, there are no reports to date of repeated measurements of in vivo cortisol responsivity in hair to transitory stressors. This issue was investigated with three males who underwent 1 min cold pressor test (CP). Cortisol response in hair to stressor demand appears to be (a) swift but transitory, (b) localized to the site of the demand and (c) independent of central HPA-axis activity.


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