Related Experiment Video

Updated: Jan 23, 2026

A BW Reporter System for Studying Receptor-Ligand Interactions

A BW Reporter System for Studying Receptor-Ligand Interactions

Published on: January 7, 2019

The pregnane X receptor and its microbiota-derived ligand indole 3-propionic acid regulate endothelium-dependent

Vivek Krishna Pulakazhi Venu^1,2, Mahmoud Saifeddine^1,3, Koichiro Mihara^1,2

¹Inflammation Research Network-Snyder Institute for Chronic Disease, Calgary, Alberta, Canada.

American Journal of Physiology. Endocrinology and Metabolism

|June 19, 2019

Abstract:

We proposed that circulating metabolites generated by the intestinal microbiota can affect vascular function. One such metabolite, indole 3-propionic acid (IPA), can activate the pregnane X receptor(PXR), a xenobiotic-activated nuclear receptor present in many tissues, including the vascular endothelium. We hypothesized that IPA could regulate vascular function by modulating PXR activity. To test this, Pxr^+/+ mice were administered broad-spectrum antibiotics for 2 wk with IPA supplementation. Vascular function was evaluated by bioassay using aorta and pulmonary artery ring tissue from antibiotic-treated Pxr^+/+ and Pxr^-/-mice, supplemented with IPA, and using aorta tissue maintained in organ culture for 24 h in the presence of IPA. Endothelium-dependent, nitric oxide(NO)-mediated muscarinic and proteinase-activated receptor 2(PAR2)-stimulated vasodilation was assessed. Endothelial nitric oxide synthase (eNOS) abundance was evaluated in intact tissue or in aorta-derived endothelial cell cultures from Pxr^+/+ and Pxr^-/- mice, and vascular Pxr levels were assessed in tissues obtained from Pxr^+/+ mice treated with antibiotics and supplemented with IPA. Antibiotic-treated Pxr^+/+ mice exhibited enhanced agonist-induced endothelium-dependent vasodilation, which was phenocopied by tissues from either Pxr^-/- or germ-free mice. IPA exposure reduced the vasodilatory responses in isolated and cultured vessels. No effects of IPA were observed for tissues obtained from Pxr^-/- mice. Serum nitrate levels were increased in antibiotic-treated Pxr^+/+and Pxr^-/- mice. eNOS abundance was increased in aorta tissues and cultured endothelium from Pxr^-/- mice. PXR stimulation reduced eNOS expression in cultured endothelial cells from Pxr^+/+ but not Pxr^-/- mice. The microbial metabolite IPA, via the PXR, plays a key role in regulating endothelial function. Furthermore, antibiotic treatment changes PXR-mediated vascular endothelial responsiveness by upregulating eNOS.

Keywords:

endothelium metabolites microbiota pregnane X receptor vasorelaxation

More Related Videos

Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery in Clinical Research

Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery in Clinical Research

Published on: October 22, 2014

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Related Concept Videos

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...

Ligand Binding Sites

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

Metal-Ligand Bonds

Metal-Ligand Bonds

The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...

Acidity and Basicity of Carboxylic Acid Derivatives

Acidity and Basicity of Carboxylic Acid Derivatives

Carboxylic acids are the strongest among organic acids, as they readily lose the hydroxyl proton to form a resonance-stabilized carboxylate ion. In comparison, the acid derivatives lack acidic hydrogens directly attached to a functional group. In these compounds, the acidic nature arises from their ability to lose α hydrogens, making them weakly acidic.
The relative acidic strength of the derivatives can be explained based on the extent of resonance stabilization of the conjugate base. The...

Internal Receptors

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.

Respiratory Regulation of Acid-Base Balance

Respiratory Regulation of Acid-Base Balance

Respiratory compensation is a vital physiological process that stabilizes blood plasma pH by regulating the partial pressure of carbon dioxide (PCO2), a key determinant of pH levels. Most carbon dioxide in the blood dissolves and converts into carbonic acid (H2CO3). It dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3⁻). There is also an inverse relationship between PCO2 and pH.
When carbon dioxide levels increase in the blood, more H+ and HCO3⁻ are...

Articles linked to this work by shared authors, journal, and citation graph.

Liquid biopsy-based detection of circulating and exfoliated cholangiocarcinoma tumor cells from blood and bile using heparan sulfate octasaccharides on integrated microfluidic systems.

Methods (San Diego, Calif.)·2026

ChatGPT-assisted pain history-taking system for musculoskeletal rehabilitation: Development and preliminary psychometric validation.

Musculoskeletal science & practice·2026

Antibiotic-induced Malassezia expansion in the infant gut promotes early-life immune dysregulation and airway inflammation in mice.

Nature communications·2026

Visualizing a lung neutrophil-platelet immunothrombosis cascade during sepsis in mice.

Science (New York, N.Y.)·2026

Stress Granule Sequestration of CCR4-NOT Promotes Poly(A) Lengthening of Stress-Survival Transcripts.

bioRxiv : the preprint server for biology·2026

Microbial 10-oxostearic acid protects mice against colitis via the nuclear receptor PPARα.

Nature microbiology·2026

See all related articles