scholarly journals Paracellular Filtration Secretion Driven by Mechanical Force Contributes to Small Intestinal Fluid Dynamics

2021 ◽  
Vol 9 (1) ◽  
pp. 9
Author(s):  
Randal K. Buddington ◽  
Thomas Wong ◽  
Scott C. Howard
Keyword(s):  
Fluid Dynamics ◽  
Small Intestine ◽  
Fluid Flow ◽  
Hydrostatic Pressure ◽  
Fluid Secretion ◽  
Mechanical Force ◽  
Pressure Gradients ◽  
Intestinal Fluid ◽  
Intact Mouse ◽  
Ion Gradients

Studies of fluid secretion by the small intestine are dominated by the coupling with ATP-dependent generation of ion gradients, whereas the contribution of filtration secretion has been overlooked, possibly by the lack of a known mechanistic basis. We measured apical fluid flow and generation of hydrostatic pressure gradients by epithelia of cultured mouse enterocytes, Caco-2 and T-84 cells, and fibroblasts exposed to mechanical force provided by vigorous aeration and in response to ion gradients, inhibitors of ion channels and transporters and in vitro using intact mouse and rat small intestine. We describe herein a paracellular pathway for unidirectional filtration secretion that is driven by mechanical force, requires tight junctions, is independent of ionic and osmotic gradients, generates persistent hydrostatic pressure gradients, and would contribute to the fluid shifts that occur during digestion and diarrhea. Zinc inhibits the flow of fluid and the paracellular marker fluorescein isothyocyanate conjugated dextran (MW = 4 kD) across epithelia of cultured enterocytes (>95%; p < 0.001) and intact small intestine (>40%; p = 0.03). We propose that mechanical force drives fluid secretion through the tight junction complex via a “one-way check valve” that can be regulated. This pathway of filtration secretion complements chloride-coupled fluid secretion during high-volume fluid flow. The role of filtration secretion in the genesis of diarrhea in intact animals needs further study. Our findings may explain a potential linkage between intestinal motility and intestinal fluid dynamics.

A novel role of intestine epithelial GABAergic signaling in regulating intestinal fluid secretion

2012 ◽  
Vol 303 (4) ◽  
pp. G453-G460 ◽  
Author(s):  
Yan Li ◽  
Yun-Yan Xiang ◽  
Wei-Yang Lu ◽  
Chuanyong Liu ◽  
Jingxin Li
Keyword(s):  
Small Intestine ◽  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Fluid Secretion ◽  
Signaling Proteins ◽  
Intestinal Epithelial ◽  
Intestinal Fluid ◽  
Patch Clamp Recording ◽  
Gaba Signaling ◽  
Intestinal Fluid Secretion

γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system, and it is produced via the enzymatic activity of glutamic acid decarboxylase (GAD). GABA generates fast biological signaling through type A receptors (GABAAR), an anionic channel. Intriguingly, GABA is found in the jejunum epithelium of rats. The present study intended to determine whether a functional GABA signaling system exists in the intestinal epithelium and if so whether the GABA signaling regulates intestinal epithelial functions. RT-PCR, Western blot, and immunohistochemical assays of small intestinal tissues of various species were performed to determine the expression of GABA-signaling proteins in intestinal epithelial cells. Perforated patch-clamp recording was used to measure GABA-induced transmembrane current in the small intestine epithelial cell line IEC-18. The fluid weight-to-intestine length ratio was measured in mice that were treated with GABAAR agonist and antagonist. The effect of GABAAR antagonist on allergic diarrhea was examined using a mouse model. GABA, GAD, and GABAAR subunits were identified in small intestine epithelial cells of mice, rats, pigs, and humans. GABAAR agonist induced an inward current and depolarized IEC-18. Both GABA and the GABAAR agonist muscimol increased intestinal fluid secretion of rats. The increased intestinal secretion was largely decreased by the GABAAR antagonist picrotoxin or gabazine, but not by tetrodotoxin. The expression levels of GABA-signaling proteins were increased in the intestinal epithelium of mice that were sensitized and challenged with ovalbumin (OVA). The OVA-treated mice exhibited diarrhea, which was alleviated by oral administration of gabazine or picrotoxin. An endogenous autocrine GABAergic signaling exists in the mammalian intestinal epithelium, which upregulates intestinal fluid secretion. The intestinal GABAergic signaling becomes intensified in allergic diarrhea, and inhibition of this GABA-signal system alleviates the allergic diarrhea.

Pressure Gradients in the Trabecular Pore Space of Femurs During Physiologic Loading

2013 ◽  
Author(s):  
Thomas A. Metzger ◽  
Stephen A. Schwaner ◽  
Glen L. Niebur
Keyword(s):  
Bone Marrow ◽  
Fluid Flow ◽  
Hydrostatic Pressure ◽  
Connective Tissue ◽  
Stromal Cells ◽  
Pore Space ◽  
Mechanical Stimuli ◽  
Pressure Gradients ◽  
Osteogenic Protein ◽  
Msc Differentiation

Bone marrow is an important niche for mesenchymal stromal cells (MSCs), which are progenitors for connective tissue cells. MSCs respond to mechanical stimuli (1). For example, steady and oscillatory fluid flow both affect MSC differentiation to the osteogenic lineages (2), while hydrostatic pressure increases MSC osteogenic protein expression (3). Both pressure and fluid flow are induced in bone marrow during loading due to the poroelastic nature of trabecular bone, and these may affect the differentiation or proliferation of the resident stromal cells.

scholarly journals Abatement of Forskolin-induced Intestinal Fluid Secretion by Modulation of Intracellular Camp With Penicillin

2021 ◽  
Author(s):  
Earnest Chen ◽  
Jason L. Own ◽  
Jenna Ollodart ◽  
Zeren Toksoy ◽  
Bruce A. Davis ◽  
...  
Keyword(s):  
Small Intestine ◽  
Gut Microbiome ◽  
Fluid Secretion ◽  
The Elderly ◽  
Penicillin G ◽  
Intracellular Camp ◽  
Protective Effects ◽  
Rat Small Intestine ◽  
Intestinal Fluid ◽  
Electrolyte Secretion

Abstract Millions of people die every year due to diarrheal related diseases, with infants and the elderly making up the majority of these deaths. Deaths are caused by excessive intestinal fluid and electrolyte secretion and are especially common in impoverished developing countries. Antibiotics have been classically used as a method to treat diarrhea-related pathologies by modulating the gut microbiome. We recently reported that penicillin may protect against disease-induced excessive fluid and electrolyte secretion via a genetics-independent, microbiome-independent mechanism in individual colonic crypt cells. In this study we investigated whether microbial-independent protective effects of penicillin against fluid secretion can be observed in the rat small intestine at the whole-tissue level. Here we report that penicillin has a significant dose-dependent protective effect against fluid secretion in induced models of diarrhea in the microbiome deficient rat small intestine. Penicillin can rapidly bring fluid secretion down to levels comparable to healthy controls. Our results suggest, for the first time, an alternative function for penicillin G as a cost-effective and fast-acting treatment against diarrheal symptoms without dependence on modulating the behavior of the existing gut microbiome.

A Computational Fluid Dynamics Study of Liquid–Solid Nano-fluid Flow in Horizontal Pipe

2021 ◽  
Author(s):  
Zainab Yousif Shnain ◽  
Jamal M. Ali ◽  
Khalid A. Sukkar ◽  
May Ali Alsaffar ◽  
Mohammad F. Abid
Keyword(s):  
Fluid Dynamics ◽  
Computational Fluid Dynamics ◽  
Fluid Flow ◽  
Horizontal Pipe ◽  
Nano Fluid
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