A xenobiotic-sensing receptor is a
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
that binds
xenobiotic
A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
s.
They include the following
nuclear receptors:
*
Constitutive androstane receptor
The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the ''NR1I3'' gene. CAR is a member of the nuclear receptor superfamily and along with pregnane ...
(CAR)
*
Pregnane X receptor
In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the ' ...
(PXR)
CAR and PXR are xenobiotic receptors and they both are members of NR1I nuclear receptor family. The regulate the metabolic pathway for the elimination of cholesterol. However, there is no physiological ligands was identified.
Xenobiotic receptors recognize the foreign chemicals and trigger detoxification and metabolism pathways in different host tissues.
Functions
Several genes involved in
cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
, phase I, and
glucuronosyltransferases conjugation catalysis in phase II are regulated by
phenobarbital(PB) as well the transport mediated pathways of drug elimination. Induction of PB in xenobiotic-metabolizes of cytochromes CYP2b undergoes a transcriptional process, thus raising mRNA levels.
Expression of the CAR summarized in a UniGene database, mainly in the kidney, liver, sometimes in the heart, GI tissues, and the human brain tissues. PB in the past ten years has been shown as an enhancer that is responsive to human(PBREM), rat(CYP2B), and the mouse; Constitutive Activated Receptor(CAR) identified was depicted to bind DR-4 motifs. The circulating thyroid hormone levels can be regulated by CAR. TH pathways of conjugation can be induced in PB treatment in a way that can lead to reductions that are fast-induced in T4 levels and serum
triiodothyronine
Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.
Production of T3 and its prohormone thyroxine ...
and finished serum thyroxine(T4).
Phase II and I enzymes PXR carries out induction. Expression of PXR is mainly evident in the liver, testis, human embryonic tissues, GI tract, and liver of the mouse. Research carried out on macrolide antibiotics, and glucocorticoids induction of CYP3A were perceived to utilize glucocorticoid receptor. This was explained by the induction of the CYP3A relationships obtained from the steroid structure-activity evaluation results. Research conducted in 1998 said that PXR was responsible for the induction of CYP3A and differences in the species in the induction of CYP3A by RIF and PCN. Based on this and other investigations, PXR has been perceived as a xenobiotic regulation mediator of CYP3A.
CAR has been depicted to be linked with a cofactor transcriptional induced by homeostasis energy regulation and fasting. Hemostasis of BA also aids in keeping the correct cholesterol levels. CAR can also impact gluconeogenesis regulation mediated by a transcription factor; the transcription factor binding can be regulated to Insulin Response Sequence(IRS). PXR protects the body from bile acid toxicity. Regarding the cholesterol levels regulation by CAR, PXR-null mice pretreatment using TCPOBOP does not reduce danger to cholesterol; therefore, toxicity from cholesterol can be controlled using PXR.
References
Receptors
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