OXGR1

Last updated
OXGR1
Identifiers
Aliases OXGR1 , GPR80, GPR99, P2RY15, P2Y15, aKGR, oxoglutarate receptor 1
External IDs OMIM: 606922; MGI: 2685145; HomoloGene: 25878; GeneCards: OXGR1; OMA:OXGR1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_080818
NM_001346194
NM_001346195
NM_001346196
NM_001346197

Contents

NM_001001490

RefSeq (protein)

NP_001333123
NP_001333124
NP_001333125
NP_001333126
NP_543008

NP_001001490

Location (UCSC) Chr 13: 96.99 – 96.99 Mb Chr 14: 120.26 – 120.28 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

OXGR1, i.e., 2-oxoglutarate receptor 1 (also known as GPR99, cysteinyl leukotriene receptor E, i.e., CysLTE, and cysteinyl leukotriene receptor 3, i.e., CysLT3 [5] [6] ) is a G protein-coupled receptor located on the surface membranes of certain cells. It functions by binding one of its ligands and thereby becoming active in triggering pre-programmed responses in its parent cells. OXGR1 has been shown to be activated by α-ketoglutarate, [7] itaconate, [8] and three cysteinyl-containing leukotrienes (abbreviated as CysLTs), leukotriene E4 (i.e., LTE4), LTC4, and LTD4. [5] [9] α-Ketoglutarate and itaconate are the dianionic forms of α-ketoglutaric acid and itaconic acid, respectively. α-Ketoglutaric and itaconic acids are short-chain dicarboxylic acids that have two carboxyl groups (notated as -CO2H) both of which are bound to hydrogen (i.e., H+). However, at the basic pH levels (i.e., pH>7) in virtually all animal tissues, α-ketoglutaric acid and itaconic acid exit almost exclusively as α-ketoglutarate and itaconate, i.e., with their carboxy residues being negatively charged (notated as -CO2), because they are not bound to H+ (see Conjugate acid-base theory). It is α-ketoglutarate and itaconate, not α-ketoglutaric or itaconic acids, which activate OXGR1. [7] [8]

History

In 2001, a human gene projected to code for a G protein-coupled receptor (i.e., a receptor that stimulates cells by activating G proteins) was identified. Its protein product was classified as an orphan receptor, i.e., a receptor whose activating ligand and function are unknown. The projected amino acid sequence of the protein encoded by this gene bore similarities to the purinergic receptor, P2Y1, and therefore might, like P2Y1, be a receptor for purines. This study named the new receptor and its gene GPR80 and GPR80, respectively. [10] Shortly thereafter, a second study found this same gene, indicated that it coded for a G protein-coupled receptor, had an amino acid sequence similar to two purinergic receptors, P2Y1 and GPR91, and determined that a large series of purine nucleotides, other nucleotides, and derivatives of these compounds did not activate this receptor. The study named this receptor GPR99. [11] A third study published in 2004 reported an orphan G protein-coupled receptor with an amino acid sequence similar to the P2Y receptor family of nucleotides was activated by two purines, adenosine and adenosine monophosphate. The study nominated this receptor to be a purinergic receptor and named it the P2Y15 receptor. [12] However, a review in 2004 of these three studies by members of the International Union of Pharmacology Subcommittee for P2Y Receptor Nomenclature and Classification decided that GPR80/GPR99 is not a receptor for adenosine, adenosine monophosphate, or any other nucleotide. [13] A fourth study, also published in 2004, found that GPR80/GPR99 -bearing cells responded to α-ketoglutarate. [14] In 2013, IUPHAR accepted this report and the names OXGR1 and OXGR1 for the α-ketoglutarate responsive receptor and its gene, respectively. [15] In 2013, a fifth study found that LTE4, LTC4, and LTD4 activated OXGR1. [5] Finally, a 2023 study provided evidence that itaconate also activated OXGR1. [8] [16]

OXGR1 gene

The human OXGR1 gene is located on chromosome 13 at position 13q32.2; that is, it resides at position 32.2 (i.e., region 3, band 2, sub-band 2) on the "q" arm (i.e., long arm) of chromosome 13. [11] [17] OXGR1 codes for a G protein coupled-receptor that is primarily linked to and activates heterotrimeric G proteins containing the Gq alpha subunit. When bound to one of its ligands, OXGR1 activates Gq alpha subunit-regulated cellular pathways (see Functions of the Gq alpha pathways) that stimulate the cellular responses that these pathways are programmed to elicit. [18] [19]

OXGR1 activating and inhibiting ligands

Activating ligands

OXGR1 is the receptor for α-ketoglutarate, LTE4, LTC4, LTD4, and itaconate. These ligands have the following relative potencies in stimulating responses in cultures of cells expressing human OXGR1: [8]

LTE4 >> LTC4 = LTD4 > α-ketoglutarate = itaconate

LTE4 is able to stimulate responses in at least some of its target cells at concentrations as low as a few picomoles/liter [5] [8] whereas LTC4, LTD4, α-ketoglutarate, and itaconate require far higher levels to do so. [6] [16]

The relative potencies that LTC4, LTD4, and LTE4 have in activating their target receptors, i.e., cysteinyl leukotriene receptor 1 (CysLTR1), cysteinyl leukotriene receptor 2 (CysLTR2), and OXGR1 are: [6]

CysLTR1: LTD4 > LTC4 >> LTE4
CysLTR2: LTC4 = LTD4 >> LTE4
OXGR1: LTE4 > LTC4 > LTD4

These relationships suggest that CysTR1 and CysLTR2 are physiological receptors for LTD4 and LTC4 but due to its relative weakness in stimulating these two receptors, perhaps not or to a far lesser extent for LTE4. Indeed, the LTE4 concentrations needed to activate CysTR1 and CysLTR2 may be higher than those that normally occur in vivo (see Functions of OXGR1 in mediating the actions of LTE4, LTD4, and LTC4). These potency relationships suggest that the LTE4's actions are mediated primarily by OXGR1. The following findings support this suggestion. First, pretreatment of guinea pig trachea and human bronchial smooth muscle with LTE4 but not with LTC4 or LTD4 enhanced their smooth muscle contraction responses to histamine. This suggests LTE4's target receptor differs from the receptors targeted by LTC4 and LTD4. Second, LTE4 was as potent as LTC4 and LTD4 in eliciting vascular leakage when injected into the skin of guinea pigs and humans; the inhalation of LTE4 by asthmatic individuals caused the accumulation of eosinophils and basophils in their bronchial mucosa whereas the inhalation of LTD4 did not have this effect; and mice engineered to lack CysLTR1 and CysLTR2 receptors exhibited edema responses to the intradermal injection of LTC4, LTD4, and LTE4 but LTE4 was 64-fold more potent in triggering this response in these mice than in wild type mice. Since LTE4 should have been far less active than LTC4 or LTD4 in triggering vascular leakage, the recruitment of the cited cells into the lung, and causing vascular edema responses in mice lacking CysLT1 and CysLT2 receptors, these findings imply that the latter two receptors are not the primary receptors mediating LTF4' actions. And third, mice engineered to lack all three CysLTR1, CysLTR2, and OXGR1 receptors did not exhibit dermal edema responses to the injection of LTC4, LTD4, or LTE4 thereby indicating that at least one of these receptors was responsible for each of their actions. Overall, these findings suggest that LTE4 commonly acts through a different receptor than LTC4 and LTD4 and that this receptor is OXGR1. [5] [9] [20] Indeed, studies have defined OXGR1 as the high affinity receptor for LTF4. [9] [21] Nonetheless, several studies have reported that cultures of certain types of inflammatory cells, e.g., the human LAD2 (but not LUVA) mast cell lines, [22] T helper cell lymphocytes that have differentiated into Th2 cells, [23] and mouse ILC2 lymphocytes (also termed type 2 innate lymphoid cells) [24] The levels of LTE4 used in some of these studies may not develop in animals or humans. In all events, dysfunctions caused by deleting the OXGR1 gene in cells, tissues or animals and dysfunctions in humans that are associated with a lack of a viable OXGR1 gene implicate the lack of OXGR1 protein in the development of these dysfunctions. [9] [22]

Inhibiting ligand

OXGR1 is inhibited by Montelukast, a well-known and clinically useful receptor antagonist, i.e., inhibitor, of CysLTR1 but not CysTR2 activation. (Inhibitors of CysLTR2 have not been identified. [25] ) In consequence, Montelukast blocks the binding and thereby the actions of LTE4, LTC4, and LTD4 that are mediated by OXGR1. It is presumed to act similarly to block the actions of α-ketoglutarate and itaconate on OXGR1. [5] [26] It is not yet known if other CysLTR1 inhibitors can mimic Montelukast in blocking OXGR1's responses to α-ketoglutarate and itaconate. Montelukast is used to treat various disorders including asthma, exercise-induced bronchoconstriction, allergic rhinitis, primary dysmenorrhea (i.e. menstrual cramps not associated with known causes, see causes of dysmenorrhea), and urticaria (see Functions of CysLTR1). While it is likely that its inhibition of CysLTR1 accounts for its effects in these diseases, the ability of these leukotrienes, particularly LTE4, to stimulate OXGR1 allows that Montelukast's effects on these conditions may be due at least in part to its ability to block OXGR1. [5]

Expression

Based on their content of the OXGR1 protein or mRNA that directs its synthesis, OXGR1 is expressed in human: a) kidney, placenta, and fetal brain; b) cells that promote allergic and other hypersensitivity reactions, i.e., eosinophils and mast cells; c) tissues involved in allergic and other hypersensitivity reactions such as the lung trachea, salivary glands, and nasal mucosa; [5] [27] [28] and d) fibroblasts, i.e., cells that synthesize the extracellular matrix and collagen (when pathologically activated, these cells produce tissue fibrosis). [25] In mice, Oxgr1 mRNA is highly expressed in kidneys, testes, smooth muscle tissues, [5] nasal epithelial cells, and lung epithelial cells. [29]

Functions

Associated with OXGR1 gene defects or deficiencies

The following studies have defined OXGR1 functions based on the presence of disorders in mice or humans that do not have a viable OXGR1 protein. It is not been determined which of OXGR1's ligands, if any, are responsible for stimulating OXGR1 to prevent these disorders.

Otitis media

Mice lacking OXGPR1 protein due the knockout of their OXGR1 gene developed (82% penetrance) otitis media (i.e., inflammation in their middle ears), mucus effusions in their middle ears, and hearing losses all which had many characteristics of human otitis media. The study did not find evidence that these mice had a middle ear bacterial infection. (Infection with Streptococcus pneumoniae, Moraxella catarrhalis , or other bacteria is one of the most common causes of otitis media. [30] ) While the underlying mechanism for the development of this otitis has not been well-defined, the study suggests that OXER1 functions to prevent middle ear inflammations and Oxgr1 gene knockout mice may be a good model to study and relate to human ear pathophysiology. [31]

Goblet cells

Mice lacking OXGR1 protein due the knockout of their OXGR1 gene had significantly fewer numbers of mucin-containing goblet cells in their nasal mucosa than control mice. Cysltr1 gene knockout mice and Cysltr2 gene knockout mice had normal numbers of these nasal goblet cells. This finding implicates OXGR1 in functioning to maintain higher numbers of airway goblet cells. [29]

Kidney stones and nephrocalcinosis

Majmunda et al. identified 6 individuals from different families with members that had histories of developing calcium-containing kidney stones (also termed nephrolithiasis) and/or nephrocalcinosis (i.e., the deposition of calcium-containing material in multiple sites throughout the kidney). Each of these 6 individuals had dominant variants in their OXGR1 gene. These variant genes appeared (based on their OXGR1 gene's DNA structure as defined by exome sequencing) to be unable to form an active OXGR1 protein. The study proposed that the OXGR1 gene is a candidate for functioning to suppress the development of calcium-containing nephrolithiasis and nephrocalcinosis in humans. [32]

Associated with α-ketoglutarate-regulated functions

Studies in rodents have found that the ability of α-ketoglutarate to regulate various functions is dependent on its activation of OXGR1 (see OXGR1 receptor-dependent bioactions of α-ketoglutarate). These functions include: promoting normal kidney functions such as the absorption of key urinary ions and maintenance of acid base balance; [33] regulating the development of glucose tolerance as defined by glucose tolerance tests; [34] suppressing the development of diet-induced obesity; [35] and suppressing the muscle atrophy response to excessive exercise. [35]

Associated with LTE4-induced functions

A study showed that LTE4, LTC4, and LTD4 produce similar levels of vascular leakage and localized tissue swelling when injected into the skin of guinea pigs or humans. Studies that examined the effects of using various doses of these LTs after injection into the earlobes of mice found that, in comparison to control mice, OXGR1 gene knockout mice showed virtually no response to injection of a low dose of LTE4, a greatly reduced response to injection of an intermediate dose of LTE4, and a somewhat delayed but otherwise similar response to a high dose of LTE4 (these doses were 0.008, 0.0625, and 0.5 nmols, respectively). The study concluded that lower levels of LTE4 act primarily through OXGR1 to cause vascular permeability and, since it is the major cysteinyl leukotriene that accumulates in inflamed tissues, suggested that OXGR1 may be a therapeutic target for treating inflammatory disorders. [5] Another study found that the application of an extract of Alternaria alternata (a genus of fungi that infects plants and causes allergic diseases, infections, and toxic reactions in animals and humans [36] ) into the noses of mice caused their nasal epithelial cells to release mucin and their nasal submucosa to swell. (The nasal as well as lung epithelial cells of these mice expressed OXGR1). OXGR1 gene knockout mice did not show these responses to the fungal toxin. The study also showed that a)Cysltr1 and Cysltr2 double gene knockout mice had full mucin release response to the toxin and b) Cstlr2 gene knockout mice had full submucosal swelling responses to the toxin but Csltr1 gene knockout mice did not show submucosal swelling responses to the toxin. The study concluded that LTE4's activation of OXGR1 controls key airway epithelial cell functions in mice and suggested that the inhibition of LTE4-induced OXGR1 activation may prove useful for treating asthma and other allergic and inflammatory disorders. [29] A subsequent study examined the effects of LTE4-OXGR1 on a certain type of tuft cell. When located in intestinal mucosa, these tuft cells are termed tuft cells but when located in the nasal respiratory mucosa they are termed solitary chemosensory cells and when located in the trachea they are termed brush cells. [37] Control mice that inhaled the mold Alternaria alternata, the American house dust mite Dermatophagoides farinae , or LTF4 developed increases in the number of their tracheal brush cells, release of the inflammation-promoting cytokine, interleukin 25, and lung inflammation whereas OXGR1 gene knockout mice did not show these responses. These findings indicate that the activation of OXGR1 regulates airway: brush cell numbers, interleukin 25 release, and inflammation. [21]

Associated with itaconate-regulated functions

A study reported in 2023 was the first and to date (2024) only study indicating that itaconate's actions are mediated by activating OXGR1. This study showed that itaconate stimulated the nasal secretion of mucus when applied to the noses of mice, reduced the number of Pseudomonas aeruginosa bacteria in their lung tissue and bronchoalveolar lavage fluid (i.e., airway washing) in mice injected intranasally with these bacteria, and stimulated cultured mouse respiratory epithelium cells to raise their cytosolic Ca2+ levels (an indicator of cell activation). Itaconate was unable to induce these responses in OXGR1 gene knockout mice or in the respiratory epithelial cells isolated from the OXGR1 gene knockout mice. The study concluded that the activation of OXGR1 by itaconate contributes to regulating the pulmonary innate immune response to Pseudomonas aeruginosa and might also do so in other bacterial infections. [8] [16]

Related Research Articles

α-Ketoglutaric acid Chemical compound

α-Ketoglutaric acid is a dicarboxylic acid, i.e., a short-chain fatty acid containing two carboxyl groups with C, O, and H standing for carbon, oxygen, and hydrogen, respectively. However, almost all animal tissues and extracellular fluids have a pH above 7. At these basic pH levels α-ketoglutaric acid exists almost exclusively as its conjugate base. That is, it has two negative electric charges due to its release of positively charged hydrogen from both of its now negatively charged carboxy groups, CO−2. This double negatively charge molecule is referred to as α-ketoglutarate or 2-oxoglutarate.

<span class="mw-page-title-main">Leukotriene</span> Class of inflammation mediator molecules

Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase.

<span class="mw-page-title-main">Lipoxin</span> Acronym for lipoxygenase interaction product

A lipoxin (LX or Lx), an acronym for lipoxygenase interaction product, is a bioactive autacoid metabolite of arachidonic acid made by various cell types. They are categorized as nonclassic eicosanoids and members of the specialized pro-resolving mediators (SPMs) family of polyunsaturated fatty acid (PUFA) metabolites. Like other SPMs, LXs form during, and then act to resolve, inflammatory responses. Initially, two lipoxins were identified, lipoxin A4 (LXA4) and LXB4, but more recent studies have identified epimers of these two LXs: the epi-lipoxins, 15-epi-LXA4 and 15-epi-LXB4 respectively.

<span class="mw-page-title-main">Itaconic acid</span> Chemical compound

Itaconic acid (also termed methylidenesuccinic acid and 2-methylidenebutanedioic acid) is a fatty acid containing five carbons (carbon notated as C), two of which are in carboxyl groups (notated as -CO2H) and two others which are double bonded together (i.e., C=C). (itaconic acid's chemical formula is C5H6O4, see adjacent figure and dicarboxylic acids). At the strongly acidic pH levels below 2, itaconic acid is electrically neutral because both of its carboxy residues are bound to hydrogen (notated as H); at the basic pH levels above 7, it is double negatively charged because both of its carboxy residues are not bound to H, i.e., CO2 (its chemical formula is C5H4O42-); and at acidic pH's between 2 and 7, it exists as a mixture with none, one, or both of its carboxy residues bound to hydrogen. In the cells and most fluids of living animals, which generally have pH levels above 7, itaconic acid exists almost exclusively in its double negatively charged form; this form of itaconic acid is termed itaconate. Itaconic acid and itaconate exist as cis and trans isomers (see cis–trans isomerism). Cis-itaconic acid and cis-itaconate isomers have two H's bound to one carbon and two residues (noted as R) bound to the other carbon in the double bound (i.e., H2C=CR2) whereas trans-itaconic acid and trans-itaconate have one H and one R residue bound to each carbon of the double bound. The adjacent figure shows the cis form of itaconic acid. Cis-aconitic acid spontaneously converts to its thermodynamically more stable (see chemical stability) isomer, trans-aconitic acid, at pH levels below 7. The medical literature commonly uses the terms itaconic acid and itaconate without identifying them as their cis isomers. This practice is used here, i.e., itaconic acid and itaconate refer to their cis isomers while the trans isomer of itaconate (which has been detected in fungi but not animals) is here termed trans-itaconate (trans-itaconic acid is not further mentioned here).

<span class="mw-page-title-main">Thromboxane receptor</span> Mammalian protein found in Homo sapiens

The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the TBXA2R gene, The thromboxane receptor is one among the five classes of prostanoid receptors and was the first eicosanoid receptor cloned. The TP receptor derives its name from its preferred endogenous ligand thromboxane A2.

An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor or leukotriene receptor antagonist and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in asthma and COPD. Leukotriene receptor antagonists are sometimes colloquially referred to as leukasts.

Leukotriene E<sub>4</sub> Chemical compound

Leukotriene E4 (LTE4) is a cysteinyl leukotriene involved in inflammation. It is known to be produced by several types of white blood cells, including eosinophils, mast cells, tissue macrophages, and basophils, and recently was also found to be produced by platelets adhering to neutrophils. It is formed from the sequential conversion of LTC4 to LTD4 and then to LTE4, which is the final and most stable cysteinyl leukotriene. Compared to the short half lives of LTC4 and LTD4, LTE4 is relatively stable and accumulates in breath condensation, in plasma, and in urine, making it the dominant cysteinyl leukotriene detected in biologic fluids. Therefore, measurements of LTE4, especially in the urine, are commonly monitored in clinical research studies.

Most of the eicosanoid receptors are integral membrane protein G protein-coupled receptors (GPCRs) that bind and respond to eicosanoid signaling molecules. Eicosanoids are rapidly metabolized to inactive products and therefore are short-lived. Accordingly, the eicosanoid-receptor interaction is typically limited to a local interaction: cells, upon stimulation, metabolize arachidonic acid to an eicosanoid which then binds cognate receptors on either its parent cell or on nearby cells to trigger functional responses within a restricted tissue area, e.g. an inflammatory response to an invading pathogen. In some cases, however, the synthesized eicosanoid travels through the blood to trigger systemic or coordinated tissue responses, e.g. prostaglandin (PG) E2 released locally travels to the hypothalamus to trigger a febrile reaction. An example of a non-GPCR receptor that binds many eicosanoids is the PPAR-γ nuclear receptor.

Leukotriene C<sub>4</sub> Chemical compound

Leukotriene C4 (LTC4) is a leukotriene. LTC4 has been extensively studied in the context of allergy and asthma. In cells of myeloid origin such as mast cells, its biosynthesis is orchestrated by translocation to the nuclear envelope along with co-localization of cytosolic phospholipase A2 (cPLA2), arachidonate 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTC4 synthase (LTC4S), which couples glutathione to an LTA4 intermediate. The MRP1 transporter then secretes cytosolic LTC4 and cell surface proteases further metabolize it by sequential cleavage of the γ-glutamyl and glycine residues off its glutathione segment, generating the more stable products LTD4 and LTE4. All three leukotrienes then bind at different affinities to two G-protein coupled receptors: CYSLTR1 and CYSLTR2, triggering pulmonary vasoconstriction and bronchoconstriction.

Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme that in humans is encoded by the ALOX5 gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase family of enzymes. It transforms essential fatty acids (EFA) substrates into leukotrienes as well as a wide range of other biologically active products. ALOX5 is a current target for pharmaceutical intervention in a number of diseases.

<span class="mw-page-title-main">GPR17</span> Protein-coding gene in the species Homo sapiens

Uracil nucleotide/cysteinyl leukotriene receptor is a G protein-coupled receptor that in humans is encoded by the GPR17 gene located on chromosome 2 at position q21. The actual activating ligands for and some functions of this receptor are disputed.

<span class="mw-page-title-main">GPR31</span> Protein in humans

G-protein coupled receptor 31 also known as 12-(S)-HETE receptor is a protein that in humans is encoded by the GPR31 gene. The human gene is located on chromosome 6q27 and encodes a G-protein coupled receptor protein composed of 319 amino acids.

<span class="mw-page-title-main">Cysteinyl leukotriene receptor 1</span> Protein-coding gene in humans

Cysteinyl leukotriene receptor 1, also termed CYSLTR1, is a receptor for cysteinyl leukotrienes (LT). CYSLTR1, by binding these cysteinyl LTs contributes to mediating various allergic and hypersensitivity reactions in humans as well as models of the reactions in other animals.

Leukotriene B<sub>4</sub> receptor 2 Protein-coding gene in humans

Leukotriene B4 receptor 2, also known as BLT2, BLT2 receptor, and BLTR2, is an Integral membrane protein that is encoded by the LTB4R2 gene in humans and the Ltbr2 gene in mice.

<span class="mw-page-title-main">Cysteinyl leukotriene receptor 2</span> Protein-coding gene in the species Homo sapiens

Cysteinyl leukotriene receptor 2, also termed CYSLTR2, is a receptor for cysteinyl leukotrienes (LT). CYSLTR2, by binding these cysteinyl LTs contributes to mediating various allergic and hypersensitivity reactions in humans. However, the first discovered receptor for these CsLTs, cysteinyl leukotriene receptor 1 (CysLTR1), appears to play the major role in mediating these reactions.

Prostaglandin EP<sub>2</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin E2 receptor 2, also known as EP2, is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the human gene PTGER2: it is one of four identified EP receptors, the others being EP1, EP3, and EP4, which bind with and mediate cellular responses to PGE2 and also, but with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). EP has been implicated in various physiological and pathological responses.

<span class="mw-page-title-main">Prostacyclin receptor</span> Mammalian protein found in Homo sapiens

The Prostacyclin receptor, also termed the prostaglandin I2 receptor or just IP, is a receptor belonging to the prostaglandin (PG) group of receptors. IP binds to and mediates the biological actions of prostacyclin (also termed Prostaglandin I2, PGI2, or when used as a drug, epoprostenol). IP is encoded in humans by the PTGIR gene. While possessing many functions as defined in animal model studies, the major clinical relevancy of IP is as a powerful vasodilator: stimulators of IP are used to treat severe and even life-threatening diseases involving pathological vasoconstriction.

The leukotriene (LT) receptors are G protein-coupled receptors that bind and are activated by the leukotrienes. They include the following proteins:

The cysteinyl leukotriene receptors (CysLTRs) include the following two receptors:

Cysteinyl-leukotriene type 1 receptor antagonists Class of drugs that hinder the action of leukotriene

Cysteinyl-leukotriene type 1 receptor antagonists, also known as CysLT1 antagonists, are a class of drugs that hinder the action of leukotriene by binding to the receptor with antagonistic action without having an agonistic effect. These drugs are used to treat asthma, relieve individuals of seasonal allergies rhinitis and prevention of exercise-induced bronchoconstriction. There are currently three different types of drugs within the CysLT1 family, zafirlukast which was first on the market being released in 1996, montelukast which was released in 1998 and pranlukast which was released in 2007.

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Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.