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Most of the eicosanoid receptors are
integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a signi ...
G protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
(GPCRs) that bind and respond to
eicosanoid Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-c ...
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 Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
to an eicosanoid which then binds cognate receptors on either its parent cell (acting as an
Autocrine signalling Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with pa ...
molecule) or on nearby cells (acting as a
Paracrine signalling Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over ...
molecule) 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 (acting as a
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
-like messenger) to trigger systemic or coordinated tissue responses, e.g. prostaglandin (PG) E2 released locally travels to the hypothalamus to trigger a febrile reaction (see ). An example of a non-GPCR receptor that binds many eicosanoids is the PPAR-γ nuclear receptor. The following is a list of human eicosanoid GPCRs grouped according to the type of eicosanoid
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
that each binds:


Leukotriene

Leukotriene 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. Leukotrienes ...
s: * BLT1 ( Leukotriene B4 receptor) – ; BLT1 is the primary receptor for
leukotriene B4 Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice. Biochemistry Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It is produced from leukocytes in respo ...
. Relative potencies in binding to and stimulating BLT1 are: leukotriene B4>20-hydroxy-leukotriene B4>> 12-Hydroxyeicosatetraenoic acid (''R'' isomer) (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=267; also see
ALOX12B Arachidonate 12-lipoxygenase, 12R type, also known as ALOX12B, 12''R''-LOX, and arachidonate lipoxygenase 3, is a lipoxygenase-type enzyme composed of 701 amino acids and encoded by the ''ALOX12B'' gene. The gene is located on chromosome 17 at po ...
and 12-Hydroxyeicosatetraenoic acid). BLT1 activation is associated with pro-inflammatory responses in cells, tissues, and animal models. * BLT2 ( Leukotriene B4 receptor 2) – ; the receptor for 12-Hydroxyheptadecatrienoic acid,
leukotriene B4 Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice. Biochemistry Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It is produced from leukocytes in respo ...
, and certain other eicosanoids and polyunsaturated fatty acid metabolites (see
BLT2 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. Discovered several years after the leukotriene B4 receptor 1 (BLT1 ...
). Relative potencies in binding to and stimulating BLT2 are: 12-hydroxyheptadecatrienoic acid (''S'' isomer)>
leukotriene B4 Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice. Biochemistry Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It is produced from leukocytes in respo ...
> 12-Hydroxyeicosatetraenoic acid (''S'' isomer)= 12-hydroperoxyeicosatetraenoic acid (''S'' isomer)> 15-Hydroxyeicosatetraenoic acid (''S'' isomer])>12-hydroxyeicosatetraenoic acid (''R'' isomer)>20-hydroxy-leukotriene LTB4 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=268). Activation of BLT2 is associated with pro-inflammatory responses by cells and tissues. * CysLT1 (
Cysteinyl leukotriene receptor 1 Cysteinyl leukotriene receptor 1, also termed CYSLTR1, is a receptor for cysteinyl leukotrienes (LT) (see leukotrienes#Cysteinyl leukotrienes). CYSLTR1, by binding these cysteinyl LTs (CysLTs; viz, LTC4, LTD4, and to a much lesser extent, LTE4) c ...
) – ;CYSLTR1 is the receptor for
Leukotriene C4 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 c ...
and
Leukotriene D4 Leukotriene D4 (LTD4) is one of the leukotrienes. Its main function in the body is to induce the contraction of smooth muscle, resulting in bronchoconstriction and vasoconstriction. It also increases vascular permeability. LTD4 is released by bas ...
; in binds and responds to leukotriene C4 more strongly than to leukotriene D4. Relative potencies for binding to and activation CYSLTR1 are: leukotriene C4≥ leukotriene D4>>leukotriene E4 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=270). Activation of this receptor is associated with pro-allergic responses in cells, tissues, and animal models. * CysLT2 (
Cysteinyl leukotriene receptor 2 Cysteinyl leukotriene receptor 2, also termed CYSLTR2, is a receptor for cysteinyl leukotrienes (LT) (see leukotrienes#Cysteinyl leukotrienes). CYSLTR2, by binding these cysteinyl LTs (CysLTs; viz, LTC4, LTD4, and to a much lesser extent, LTE4) ...
) – ; Similar to CYSLTR1, CYSLTR2 is the receptor for
Leukotriene C4 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 c ...
and
Leukotriene D4 Leukotriene D4 (LTD4) is one of the leukotrienes. Its main function in the body is to induce the contraction of smooth muscle, resulting in bronchoconstriction and vasoconstriction. It also increases vascular permeability. LTD4 is released by bas ...
; it binds and responds to the latter two ligands equally well. Relative potencies in binding to and stimulating CYSLTR2 are: leukotriene C4≥leukotriene D4>>leukotriene E4 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=270). CYSLT2 Activation of this receptor is associated with pro-allergic responses in cells, tissues, and animal models. * GPR99/OXGR1 – ; GPR99, also known as the 2-oxoglutarate receptor 1 (OXGR1) or cysteinyl leukotriene receptor E (CysLTE), is a third CysLTR receptor; unlike CYSLTR1 and CYSLTR2, GPR99 binds and responds to
Leukotriene E4 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 pr ...
much more strongly than to leukotriene C4 or leukotriene D4. GPR99 is also the receptor for alpha-ketoglutarate, binding and responding to this ligand much more weakly than to any of the three cited leukotrienes. Activation of this receptor by LTC4 is associated with pro-allergic responses in cells and an animal model. The function of GPR99 as a receptor for leukotriene E4 has been confirmed in a mouse model of allergic rhinitis. *
GPR17 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 dis ...
– ; while one study reported that
leukotriene C4 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 c ...
,
leukotriene D4 Leukotriene D4 (LTD4) is one of the leukotrienes. Its main function in the body is to induce the contraction of smooth muscle, resulting in bronchoconstriction and vasoconstriction. It also increases vascular permeability. LTD4 is released by bas ...
, and
leukotriene E4 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 pr ...
bind to and activate GPR17 with equal potencies, many subsequent studies did not confirm this. GPR17, which is mainly expressed in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
, has also been reported to be the receptor for the purines,
Adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...
and
Uridine diphosphate Uridine diphosphate, abbreviated UDP, is a nucleotide diphosphate. It is an ester of pyrophosphoric acid with the nucleoside uridine. UDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase uracil. UDP is an importa ...
, and certain glycosylated uridine diphosphate purines (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=88) as well as to be involved in animal models of central nervous system
Demyelinating Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...
reactions. However, recent reports failed to confirm the latter findings; a consensus of current opinion holds that the true ligand(s) for GPR17 remain to be defined (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=88).


Lipoxin

Lipoxins 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-resolv ...
: * ALX/FPR2 (also termed
FPR2 N-formyl peptide receptor 2 (FPR2) is a G-protein coupled receptor (GPCR) located on the surface of many cell types of various animal species. The human receptor protein is encoded by the ''FPR2'' gene and is activated to regulate cell function b ...
, ALX, ALX/FPR, formyl peptide receptor-like 1) – ; receptor for
Lipoxin 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-resolvin ...
A4 and 15-epi-Lipoxin A4 (or AT-LxA4) eicosanoids but also many other agents including the
docosanoid In biochemistry, docosanoids are signaling molecules made by the metabolism of twenty-two-carbon fatty acids (EFAs), especially the omega-3 fatty acid, Docosahexaenoic acid (DHA) (i.e. 4''Z'',7''Z'',10''Z'',13''Z'',16''Z'',19''Z''-docosahexaenoic a ...
s
resolvin Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as docosapentaenoic acid (DPA) and clupanodonic acid. As autacoids similar t ...
D1, resolvin D2, and 17R-resolvin D1 (see
specialized pro-resolving mediators Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of ...
; oligopeptides such as
N-Formylmethionine-leucyl-phenylalanine ''N''-Formylmethionyl-leucyl-phenylalanine (fMLF, fMLP or ''N''-formyl-met-leu-phe) is an ''N''- formylated tripeptide and sometimes simply referred to as chemotactic peptide is a potent polymorphonuclear leukocyte (PMN) chemotactic factor and ...
; and various proteins such as the amino acid 1 to 42 fragment of
Amyloid beta Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...
,
Humanin Humanin is a micropeptide encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2. Its structure contains a three-turn α-helix, and no symmetry. In ''in vitro'' and animal models, it appears to have cytoprotective effects. ...
, and the N-terminally truncated form of the chemotactic chemokine,
CCL23 Chemokine (C-C motif) ligand 23 (CCL23) is a small cytokine belonging to the CC chemokine family that is also known as Macrophage inflammatory protein 3 (MIP-3) and Myeloid progenitor inhibitory factor 1 (MPIF-1). CCL23 is predominantly expresse ...
(see FPR2#Ligands and ligand-based disease-related activities). Relative potencies in binding to and activating ALX/FPR are: lipoxin A4=aspirin-triggered lipoxin A4>
leukotriene C4 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 c ...
=
leukotriene D4 Leukotriene D4 (LTD4) is one of the leukotrienes. Its main function in the body is to induce the contraction of smooth muscle, resulting in bronchoconstriction and vasoconstriction. It also increases vascular permeability. LTD4 is released by bas ...
>>15-deoxy-LXA4>>N-Formylmethionine-leucyl-phenylalanine (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=223}. Activation of ALX/FPR2 by the lipoxins is associated with anti-inflammatory responses by target cells and tissues. Receptors that bind and respond to a wide range of ligands with such seemingly different structural similarities as those of ALX/FPR are often termed promiscuous.


Resolvin E

Resolvin Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as docosapentaenoic acid (DPA) and clupanodonic acid. As autacoids similar t ...
Es: *
CMKLR1 Chemokine like receptor 1 also known as ChemR23 (Chemerin Receptor 23) is a protein that in humans is encoded by the ''CMKLR1'' gene. Chemokine receptor-like 1 is a G protein-coupled receptor for the chemoattractant adipokine chemerin and the ome ...
– ; CMKLR1, also termed Chemokine like receptor 1 or ChemR23, is the receptor for the eicosanoids
resolvin Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as docosapentaenoic acid (DPA) and clupanodonic acid. As autacoids similar t ...
E1 and 18S-resolvin E2 (see
specialized pro-resolving mediators Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of ...
) as well as for
chemerin Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a protein that in humans is encoded by the ''RARRES2'' gene. Function Retinoids exert b ...
, an
adipokine The adipokines, or adipocytokines (Greek ', fat; ', cell; and ', movement) are cytokines (cell signaling proteins) secreted by adipose tissue. Some contribute to an obesity-related low-grade state of inflammation or to the development of metabolic ...
protein; relative potencies in binding to and activating CMKLR1 are: resolvin E1>chemerin C-terminal peptide>18''R''-hydroxy-eicosapentaenoic acid (18''R''-EPE)>eicosapentaenoic acid (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=79). Apparently, the resolvins activate this receptor in a different manner than chemerin: resolvins act through it to suppress while chemerin acts through it to stimulate pro-inflammatory responses in target cells


Oxoeicosanoid

Oxoeicosanoid The oxoeicosanoids are nonclassic eicosanoids, derived from arachidonic acid (AA). For example, Lipoxygenase produces 5-HETE from AA; a dehydrogenase then produces 5-oxo-eicosatetraenoic acid, an oxoeicosanoid, from 5-HETE. They are similar to ...
: * Oxoeicosanoid (OXE) receptor 1 – ; OXER1 is the receptor for 5-oxo-eicosatetraenoic acid (5-oxo-ETE) as well as certain other eicosanoids and long-chain polyunsaturated fatty acids that possess a 5-hydroxy or 5-oxo residue (see 5-Hydroxyeicosatetraenoic acid); relative potencies of the latter metabolites in binding to and activating OXER1 are: 5-oxoicosatetraenoic acid>5-oxo-15-hydroxy-eioxatetraenoic acid> 5''S''-hydroperoxy-eicosatetraenoic acid> 5-Hydroxyeicosatetraenoic acid; the 5-oxo-eicosatrienoic and 5-oxo-octadecadienoic acid analogs of 5-oxo-ETE are as potent as 5-oxo-ETE in stimulating this receptor (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=271). Activation of OXER1 is associated with pro-inflammatory and pro-allergic responses by cells and tissues as well as with the proliferation of various human cancer cell lines in culture.


Prostanoid

Prostanoid Prostanoids are active lipid mediators that regulate inflammatory response. Prostanoids are a subclass of eicosanoids consisting of the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconst ...
s and
Prostaglandin receptors Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane receptors that are regarded as the primary receptors for one or more of the classical, naturally occurring prostanoids viz., prostaglandin D2, (i.e. PGD2) ...
Prostanoids are
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
s (PG),
thromboxane Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring. Thromboxane is named for its ...
s (TX), and
prostacyclin Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprosteno ...
s (PGI). Seven, structurally-related, prostanoid receptors fall into three categories based on the cell activation pathways and activities which they regulate. Relaxant prostanoid receptors (IP, DP1, EP2, and EP4) raise cellular
cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
levels; contractile prostanoid receptors (TP, FP, and EP1) mobilize intracellular calcium; and the inhibitory prostanoid receptor (EP3) lowers cAMP levels. A final prostanoid receptor, DP2, is structurally related to the
chemotaxis Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...
class of receptors and unlike the other prostanoid receptors mediates
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
,
basophil Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
, and
T helper cell The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
(Th2 type) chemotactic responses. Prostanoids, particularly PGE2 and PGI2, are prominent regulators of inflammation and allergic responses as defined by studies primarily in animal models but also as suggested by studies with human tissues and, in certain cases, human subjects. *PGD2: DP-(PGD2) ( PGD2 receptor) **DP1 (
PTGDR1 The Prostaglandin D2 receptor 1 (DP1), a G protein-coupled receptor encoded by the ''PTGDR1'' gene (also termed ''PTGDR''), is primarily a receptor for prostaglandin D2 (PGD2). The receptor is a member of the Prostaglandin receptors belonging to ...
) – ; DP1 is a receptor for
Prostaglandin D2 Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR (DP1), as well as CRTH2 (DP2). It is a major prostaglandin produced by mast cells – recruits Th2 cells, eosinophils, and basophils. In mammalian organs, large amou ...
; relative potencies in binding to and activating DP1 for the following prostanoids are: PGD2>>PGE2>PGF2α>PGI2=TXA2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=338). Activation of DP2 is associated with the promotion of inflammatory and the early stage of allergic responses; in limited set of circumstances, however, DP1 activation may ameliorate inflammatory responses. **DP2 (
PTGDR2 Prostaglandin D2 receptor 2 (DP2 or CRTH2) is a human protein encoded by the PTGDR2 gene and GPR44. DP2 has also been designated as CD294 (cluster of differentiation 294). It is a member of the class of prostaglandin receptors which bind with and ...
) – ; DP2, also termed CRTH2, is a receptor for prostaglandin D2; relative potencies in binding to and stimulating PD2 are PGD2 >>PGF2α, PGE2>PGI2=TXA2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=339&familyId=58&familyType=GPCR). While DP1 activation causes the chemotaxis of pro-inflammatory cells such as basophils, eosinophils, and T cell lymphocytes, its deletion in mice is associated with a reduction in an acute allergic responses in a rodent model. This and other observations suggest that DP2 and DP1 function to counteract each other. * PGE2: EP-(PGE2) ( PGE2 receptor) ** EP1-(PGE2) (
PTGER1 Prostaglandin E2 receptor 1 (EP1) is a 42kDa prostaglandin receptor encoded by the PTGER1 gene. EP1 is one of four identified EP receptors, EP1, EP2, EP3, and EP4 which bind with and mediate cellular responses principally to prostaglandin E2) (PG ...
) – ; EP1 is a receptor for
prostaglandin E2 Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and ...
; relative potencies in binding to and stimulating EP1 are PGE2>PGF2α=PGI2>PGD2=TXA2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=346&familyId=58&familyType=GPCR). EP1 activation is associated with the promotion of inflammation, particularly in the area of inflammation-based pain perception, and asthma, particularly in the area of airways constriction. ** EP2-(PGE2) (
PTGER2 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 ...
) – ; EP2 is a receptor for prostaglandin E2; relative potencies in binding to and stimulating EP2 are PGE2>PGF2α=PGI2>PGD2=TXA2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=341). EP2 activation is associated with the suppression of inflammation and inflammation-induced
pulmonary fibrosis Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failu ...
reactions as well as allergic reactions. ** EP3-(PGE2) (
PTGER3 Prostaglandin EP3 receptor (53kDa), also known as EP3, is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the human gene PTGER3; it is one of four identified EP receptors, the others being EP1, EP2, and EP4, all of which bind wit ...
) – ; EP3 is a receptor for prostaglandin E2; relative potencies in binding to and stimulating EP3 are PGE2>PGF2α=PGI2>PGD2+TXA2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=342). Activation of EP3 is associated with the suppression of the early and late phases of allergic responses; EP3 activation is also responsible for febrile responses to inflammation. ** EP4-(PGE2) (
PTGER4 Prostaglandin E2 receptor 4 (EP4) is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the PTGER4 gene in humans; it is one of four identified EP receptors, the others being EP1, EP2, and EP3, all of which bind with and mediate cell ...
) – ; EP4 is a receptor for prostaglandin E2; relative potencies in binding to and stimulating EP4 are PGE2>PGF2α=PGI2>PGD2=TXA2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=343). EP4, particularly in association with EP2, activation is critical for the development of arthritis in different animal models. * PGF: FP-(PGF) (
PTGFR Prostaglandin F receptor (FP) is a receptor belonging to the prostaglandin (PG) group of receptors. FP binds to and mediates the biological actions of Prostaglandin F2α (PGF2α). It is encoded in humans by the ''PTGFR'' gene. Gene The ''P ...
) – ; FP is the receptor for prostaglandin F2 alpha; relative potencies in binding to and stimulating FP are PGF2α>PGD2>PGE2>PGI2=thromboxane A2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=344). This receptor is the least selective of the prostanoid receptors in that both PGD2 and PGE2 bind to and stimulate it with potencies close to that of PGF2α. FP has two
splice variant Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...
s, FPa and FPb, which differ in the length of their
C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
tails. PGF2α-induced activation of FP has pro-inflammatory effects as well as roles in ovulation, luteolysis, contraction of uterine smooth muscle, and initiation of parturition. Analogs of PGF2α have been developed for estrus synchronization, abortion in domestic animals, influencing human reproductive function, and reducing intraocular pressure in glaucoma. * PGI2 (
prostacyclin Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprosteno ...
): IP-(PGI2) (
PTGIR 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, ...
) – ; IP is the receptor for
prostacyclin Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprosteno ...
I2; relative potencies in binding to and stimulating IP are: PGI2>>PGD2= PGE2=PGF2α>TXA2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=345). Activation of IP is associated with the promotion of capillary permeability in inflammation and allergic responses as well as partial suppression of experimental arthritis in animal models. IP is expressed in at least three
alternatively spliced Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...
isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
s which differ in the length of their C-terminus and which also activate different cellular signaling pathways and responses. * TXA2 (
thromboxane Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring. Thromboxane is named for its ...
): TP-(TXA2) (
TBXA2R 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 rec ...
) – ; TP is the receptor for
thromboxane A2 Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets during hemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by act ...
; relative potencies in binding to and stimulating TP are TXA2=PGH2>>PGD2=PGE2=PGF2α=PGI2 (http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=346&familyId=58&familyType=GPCR). In addition to PGH2, several
isoprostane The isoprostanes are prostaglandin-like compounds formed ''in vivo'' from the free radical-catalyzed peroxidation of essential fatty acids (primarily arachidonic acid) without the direct action of cyclooxygenase (COX) enzymes. The compounds were d ...
s have been found to be potent stimulators of and to act in part through TP. The TP receptor is expressed in most human cells types as two
alternatively spliced Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...
isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
s, TP receptor-α and TP receptor β, which differ in the length of their C-terminus tail; these isoforms communicate with different G proteins, undergo heterodimerization, and thereby result in different changes in intracellular signaling (only the TP receptor α is expressed in mice). Activation of TP by TXA2 or isoprostanes is associated with pro-inflammatory responses in cells, tissues, and animal models. TP activation is also associated with the promotion of
platelet aggregation Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
and thereby
blood clotting Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
and
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...
.


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* * * {{Cannabinoidergics G protein-coupled receptors