PAF receptor | Platelet-activating factor receptor | IUPHAR/BPS Guide to PHARMACOLOGY

PAF receptor

Target id: 334

Nomenclature: PAF receptor

Family: Platelet-activating factor receptor

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     PAF receptor has curated GtoImmuPdb data

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 342 1p35-p34.3 PTAFR platelet activating factor receptor 10,36,49,60,64
Mouse 7 341 D2.2 Ptafr platelet-activating factor receptor 30
Rat 7 341 5q36 Ptafr platelet-activating factor receptor 7
Previous and Unofficial Names
PAFr | AGEPC receptor
Database Links
Specialist databases
GPCRDB ptafr_human (Hs), ptafr_mouse (Mm), ptafr_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
methylcarbamyl PAF
PAF

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]PAF Hs Full agonist 8.8 – 8.9 pKd 22,49
pKd 8.8 – 8.9 (Kd 1.6x10-9 – 1.3x10-9 M) [22,49]
PAF Hs Full agonist 7.5 – 7.9 pKi 49,52
pKi 7.5 – 7.9 [49,52]
PAF Hs Full agonist 8.2 pIC50 3
pIC50 8.2 [3]
2-O-ethyl-PAF C-16 Hs Full agonist 7.7 pIC50 3
pIC50 7.7 [3]
2-O-methyl-PAF C-18 Hs Full agonist 5.8 pIC50 3
pIC50 5.8 [3]
enantio PAF C-16 Hs Full agonist 5.0 pIC50 3
pIC50 5.0 [3]
Agonist Comments
Some oxidised phospholipids (oxLDL) also behave as agonists at the PAF receptor [6,40,56,62], reviewed in [41] and [43]. In a murine model of melanoma, oxidised glycerophosphocholines (ox-GPCs) with PAF receptor agonist activity may enhance tumour growth by targeting host immune cells [58]. Enhanced clearance of damaged or altered cells (eg apoptotic cells) by phagocytosis has been reported to involve direct interaction of the PAF receptor on phagocytes and PAF-like molecules on the cell surface of the apoptotic cells [14].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
PCA 4248 Hs Antagonist 7.4 pA2 19
pA2 7.4 Displacement of [3H]PAF binding to polymorphonuclear cells. [19]
[3H]52770 RP Hs Antagonist 8.4 pKd 42
pKd 8.4 [42]
[3H]apafant Hs Antagonist 7.4 – 8.0 pKd 3,22,49
pKd 7.4 – 8.0 [3,22,49]
foropafant Hs Antagonist 10.3 pKi 25
pKi 10.3 [25]
ABT-299 Hs Antagonist 9.5 pKi 1
pKi 9.5 [1]
ABT-491 Hs Antagonist 9.2 pKi 2
pKi 9.2 [2]
RP-52770 Hs Antagonist 8.2 pKi 42
pKi 8.2 [42]
L659989 Hs Antagonist 7.8 pKi 28
pKi 7.8 (Ki 1.43x10-8 M) [28]
10-OBn-7α-F-gingkolide B Mm Antagonist 7.0 pKi 71
pKi 7.0 [71]
7α-Cl-ginkgolide B Mm Antagonist 7.0 pKi 71
pKi 7.0 [71]
10-OBn-ginkgolide B Mm Antagonist 6.9 pKi 71
pKi 6.9 [71]
BN 50739 Hs Antagonist 6.9 pKi 66
pKi 6.9 [66]
apafant Hs Antagonist 5.2 – 7.5 pKi 52,66
pKi 5.2 – 7.5 [52,66]
7α-N3-ginkgolide B Mm Antagonist 6.3 pKi 71
pKi 6.3 [71]
10-OBn-epi-ginkgolide C Mm Antagonist 6.2 pKi 71
pKi 6.2 [71]
7α-NHMe-ginkgolide B Mm Antagonist 6.2 pKi 71
pKi 6.2 [71]
ginkgolide B Mm Antagonist 6.1 – 6.2 pKi 63,71
pKi 6.1 – 6.2 [63,71]
7α-F-ginkgolide B Mm Antagonist 6.0 pKi 71
pKi 6.0 [71]
10-OBn-ginkgolide C Mm Antagonist 5.8 pKi 71
pKi 5.8 [71]
7α-NHEt-ginkgolide B Mm Antagonist 5.8 pKi 71
pKi 5.8 [71]
ginkgolide A Mm Antagonist 5.8 pKi 63
pKi 5.8 [63]
7α-OCOCH2Ph-ginkgolide B Mm Antagonist 5.6 pKi 71
pKi 5.6 [71]
7-epi-ginkgolide C Mm Antagonist 5.4 pKi 71
pKi 5.4 [71]
7α-NH2-ginkgolide B Mm Antagonist 5.1 pKi 71
pKi 5.1 [71]
7α-OAc-ginkgolide B Mm Antagonist 5.1 pKi 71
pKi 5.1 [71]
ginkgolide J Mm Antagonist 5.0 pKi 63
pKi 5.0 [63]
ginkgolide C Mm Antagonist 4.9 pKi 63
pKi 4.9 [63]
israpafant Hs Antagonist 9.0 pIC50 49
pIC50 9.0 [49]
CV-6209 Hs Antagonist 8.1 – 8.3 pIC50 23,49
pIC50 8.1 – 8.3 [23,49]
SDZ 64-412 Hs Antagonist 7.2 pIC50 24
pIC50 7.2 [24]
CV-3988 Hs Antagonist 6.8 pIC50 68
pIC50 6.8 (IC50 1.6x10-7 M) [68]
SCH 37370 Hs Antagonist 6.2 pIC50 35
pIC50 6.2 [35]
SCH 40338 Hs Antagonist 6.2 pIC50 35
pIC50 6.2 [35]
PCA 4248 Hs Antagonist 5.4 pIC50 19
pIC50 5.4 (IC50 3.6x10-6 M) Inhibition of PAF-induced platelet aggregation. [19]
bepafant Hs Antagonist 3.6 – 6.5 pIC50 19,26
pIC50 6.1 – 6.5 (IC50 8.3x10-7 – 3.2x10-7 M) Inhibition of PAF-induced platelet or neutrophil aggregation. [26]
pIC50 3.6 – 6.5 (IC50 2.5x10-4 – 3x10-7 M) Induction of apoptosis in human NB4 (acute promyelocytic leukemia) cells. [19]
View species-specific antagonist tables
Antagonist Comments
The above binding assays were performed using transfected cells, except references [1-2,24] which measured binding to preparations of platelet membranes, reference [42] which measured binding to human polymorphonuclear leukocytes and reference [35] which measured the inhibition of platelet aggregation.

The above table lists a small selection of the known PAF receptor antagonists. For reviews on PAF receptor antagonists see [13,65].
Immunopharmacology Comments
PAF deficiency results in defective inflammatory response to infection in mice.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 6 GO processes
GO:0006954 inflammatory response TAS
GO:0043312 neutrophil degranulation TAS
GO:0060333 interferon-gamma-mediated signaling pathway TAS
click arrow to show/hide IEA associations
GO:0001875 lipopolysaccharide receptor activity IEA
GO:0043315 positive regulation of neutrophil degranulation IEA
GO:1903238 positive regulation of leukocyte tethering or rolling IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 4 GO processes
GO:0060333 interferon-gamma-mediated signaling pathway TAS
click arrow to show/hide IEA associations
GO:0001816 cytokine production IEA
GO:0032760 positive regulation of tumor necrosis factor production IEA
GO:0045410 positive regulation of interleukin-6 biosynthetic process IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0043312 neutrophil degranulation TAS
click arrow to show/hide IEA associations
GO:0001875 lipopolysaccharide receptor activity IEA
GO:0043315 positive regulation of neutrophil degranulation IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001875 lipopolysaccharide receptor activity IEA
GO:0043315 positive regulation of neutrophil degranulation IEA
GO:1903238 positive regulation of leukocyte tethering or rolling IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:1903238 positive regulation of leukocyte tethering or rolling IEA
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G protein independent mechanism
Adenylate cyclase stimulation
Other - See Comments
Comments:  Other=Janus kinase/STAT
References:  8,16,37-38,56
Tissue Distribution
Bone marrow stromal cells.
Species:  Human
Technique:  RT-PCR.
References:  17
Spermatozoa (proximal head, midpiece >> distal head, tail).
Species:  Human
Technique:  Immunofluorescent microscopy.
References:  54
Fallopian tubes.
Species:  Human
Technique:  RT-PCR and Western blotting.
References:  70
Dorsal root ganglion and spinal cord.
Species:  Mouse
Technique:  RT-PCR.
References:  45
Spleen > skeletal muscle, thioglycollate elicited macrophages > small intestine > resident peritoneal macrophages > lung > heart > liver > kidney > brain.
Species:  Mouse
Technique:  Northern blotting.
References:  30
Cerebral cortex (intense signals scattered randomly in all of the layers, moderate signals found in layers II-VI), olfactory bulb, hippocampus (intense signals scattered randomly, moderate signals found in the pyramidal cell layer and dentate gyrus), medial thalamus, hypothalamus, and cerebellum (intense signals were scattered randomly, slight to moderate signals were found in the granular cell and Purkinje cell layers).
Species:  Rat
Technique:  in situ hybridisation.
References:  44
Microglia.
Species:  Rat
Technique:  in situ hybridisation, Northen blotting and RT-PCR.
References:  44
Kidney: glomerulus > proximal convoluted tubule > proximal straight tubule > cortical collecting duct, outer medullary collecting duct, distal convoluted tubule > cortical thick ascending limb, medullary thick ascending limb.
Species:  Rat
Technique:  RT-PCR.
References:  4
Spleen > small intestine > kidney > lung > liver >> pancreas >> brain.
Species:  Rat
Technique:  Northern blotting.
References:  7
Pancreatic microvascular endothelial cells.
Species:  Rat
Technique:  Immunohistochemistry.
References:  21
Expression Datasets

Show »

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays
Measurement of FAK (Focal Adhesion Kinase) activity in HUVECs.
Species:  Human
Tissue:  HUVECs.
Response measured:  FAK activation via Gαq upon application of an agonist.
References:  16
Measurement of membrane potential in Xenopus oocytes transfected with the human PAF recptor.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Production of an inward current upon application of an agonist.
References:  49
Measurement of IP3 levels in COS-7 cells transfected with the human PAF receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Accumulation of IP3 upon application of an agonist.
References:  49
Measurement of membrane potential in Xenopus oocytes transfected with the human PAF receptor.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Production of a Ca2+-activated Cl- current upon application of an agonist.
References:  64
Measurement of membrane potential in Xenopus oocytes transfected with the rat PAF receptor.
Species:  Rat
Tissue:  Xenopus oocytes.
Response measured:  Cl- channel opening.
References:  7
Measurement of cAMP levels in Human Umbilical Vein Endothelial cells (HEVECs) endogenously expressing the PAF receptor.
Measurement of PKA activity and subsequent signalling to Src.
Species:  Human
Tissue:  HUVECs.
Response measured:  Increase in cAMP levels via Gαq, subsequent increase in PKA activity and signalling to Src, upon application of an agonist.
References:  16
Measurement of PLCβ3 activity in HUVECs.
Species:  Human
Tissue:  HUVECs.
Response measured:  PLCβ3 activation via Gαq upon application of agonist.
References:  16
Measurement of Ca2+ mobilisation in CHO cells transfected with the wild-type receptor or the Ala224 -> Asp substituted mutant PAF receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Equivalent Ca2+ mobilisation in both the wild-type and mutant receptors.
References:  22
Measurement of IP3 and cAMP levels in CHO cells transfected with the wild-type receptor or the Ala224 -> Asp substituted mutant PAF receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  IP3 production and inhibition of cAMP accumulation upon activation of the wild-type receptor. Both reduced with the mutant receptor.
References:  22
Measurement of chemotactic activity in CHO cells transfected with either the wild-type or the Ala224 -> Asp substituted mutant PAF receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Reduced chemotactic index with the mutant receptor.
References:  22
Measurement of Ca2+ levels in isolated rat microglial cells using fluorometric Ca2+ imaging.
Species:  Rat
Tissue:  Isolated microglia.
Response measured:  Elevated [Ca2+]i in response to PAF.
References:  44
Measurement of Ca2+ levels in cultured rat hippocampal cells using fluorometric Ca2+ imaging.
Species:  Rat
Tissue:  Cultured hippocampal cells.
Response measured:  Elevated [Ca2+]i in response to PAF.
References:  44
Measurement of arachidonic acid levels in isolated rat microglial cells endogenously expressing the PAF receptor.
Species:  Rat
Tissue:  Isolated microglia.
Response measured:  Arachidonic acid release is response to PAF.
References:  44
Physiological Functions
Vasodilation.
Species:  Rat
Tissue:  Mesenteric arterial bed.
References:  34
Superoxide production.
Species:  Human
Tissue:  Eosinophils.
References:  5
Cell proliferation, motility and angiogenic response.
Species:  Human
Tissue:  Breast cancer cells.
References:  9
Enhancement of excitatory synaptic transmission.
Species:  Rat
Tissue:  Cultured hippocampal neurons.
References:  12
PAF receptor activation may be an initiator of neuronal dysfunction and cell death involved with HIV-1 associated dementia.
Species:  Human
Tissue:  Primary neurons.
References:  53
Cell aggregation.
Species:  Human
Tissue:  Leukocytes and platelets.
References:  15
Regulation of angiogenesis and inflammatory response.
Species:  Mouse
Tissue:  In vivo
References:  20
Mediation of lipopolysaccharide (LPS)-induced systemic inflammation.
Species:  Rat
Tissue:  In vivo.
References:  33
Parasite phagocytosis.
Species:  Mouse
Tissue:  Cardiac tissue.
References:  67
Upregulation of bradykinin B1 receptors as measured by bradykinin-induced oedema.
Species:  Rat
Tissue:  In vivo.
References:  18
Intrathecal administration of PAF induces tactile allodynia (pain induced from normally non-painful stimuli) and thermal hyperalgesia at the level of the spinal cord.
Species:  Mouse
Tissue:  In vivo.
References:  45
Neovascularisation (thought to be linked to the PAF-induced upregulation of angiogenic factors VEGF and FGF-2 as found in HUVECs).
Species:  Mouse
Tissue:  Cornea.
References:  39
Bronchoconstiction via the production of thromboxane A2, LTC4, LTD4 and LTE4.
Species:  Mouse
Tissue:  Airway smooth muscle.
References:  46
Platelet aggregation.
There appears to be a synergistic interaction between 5-HT and PAF on platelet aggregation, TXA2 formation and ERK1/2 phosphorylation. It is thought to involve PLC/Ca2+, COX and MAPK pathways.
Species:  Human
Tissue:  Platelets.
References:  61
Physiological Consequences of Altering Gene Expression
Transgenic mice overexpressing the PAF receptor exhibit enhanced acid aspiration-induced lung injury and respitatory failure.
PAF receptor knockout mice exhibit reduced acid aspiration-induced lung injury and respitatory failure.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  47
PAF receptor knockout mice exhibit reduced anaphylactic symptoms, although normal neuronal development, reproduction and responses to bacterial endotoxin.
A possible use for PAF receptor antagonists could be to prevent anaphylactic responses without serious side-effects.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  29
PAF receptor knockout mice exhibit a decreased airway hyperresponsiveness to muscarinic cholinergic stimulation in an asthma model, although no difference to the eosinophilic inflammatory response when compared to the wild-type.
This suggests that PAF acts downstream of the airway inflammation in brionchial asthma.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  31
PAF receptor knockout mice and wild-type mice were innoculated intranasally with S. pneumoniae. The knockout mice had an increased resistance to pneumococcal pneumonia compared to the wild-type mice.
This study suggests that S. pneumoniae uses the PAF receptor to induce pneumonia.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  55
The embryos of PAF receptor knockout mice show an increase in the thickness of the external granular layer of the cerebellum.
In vitro studies using cerebellar granule neurons from PAF receptor knockout mice show reduced migration when compared to wild-type neurons.
However, PAF still had some effect on the migration of the wild-type neurons, suggesting an additional receptor-independent pathway for PAF.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  69
PAF receptor knockout mice are found to be protected from the spacial learning deficits, increased oxidative stress, inflammatory signalling and apoptosis that are associated with intermittent hypoxia (IH) during sleep.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  57
PAF receptor knockout mice exhibit reduced high frequency stimulation-induced LTP in hippocampal dentate gyrus cells compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11
PAF receptor knockout mice and wild-type mice were infected with Strongyloides venezuelensis. The PAF receptor knockout mice exhibited a decrease in inflammatory response and subsequent delay in worm elimination. They also showed a reduction in the number of eggs produced by the worms, suggesting that PAF receptor-mediated responses may effect egg output.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  50
Transgenic mice overexpressing the PAF receptor exhibit epidermal hyperproliferation and an increase in dermal melanocytes. The PAF receptor gene was found in keratinocytes, not melanocytes, suggesting that the receptor has a role in the growth of epidermal keratinocytes.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  59
Comparison of PAF receptor knockout mice and wild-type mice following ovariectomies suggested that the PAF receptor links eostrogen depletion with osteoporosis.
It is suggested that a reduction in eostrogen enhances PAF production. In wild-type mice this alters osteoclast cell functions and leads to bone resorption. In PAF receptor knockout mice this bone loss is reduced.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27
PAF receptor knockout mice exhibit increased angiogenesis and decreased inflammation in comparison to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  20
PAF receptor knockout mice infected with the hemoflagellate parasite Trypanosoma cruzi exhibited increased parasite replication and increased inflammatory response.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  67
Transgenic mice overexpressing the PAF receptor exhibited bronchoconstiction mediated via the PAF-induced production of thromboxane A2 and and cysteneinly leukotrienes LTC4, LTD4 and LTE4.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  46
Transgenic mice overexpressing the PAF receptor exhibit hyperresponsiveness to metacholine and PAF, blocked by atropine. This suggests that this hyperresponsiveness may involve the muscarinic pathway.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  48
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ptafrtm1Eit Ptafrtm1Eit/Ptafrtm1Eit
involves: C57BL/6
MGI:106066  MP:0005167 abnormal blood-brain barrier function PMID: 16299272 
Ptafrtm1Eit Ptafrtm1Eit/Ptafrtm1Eit
involves: C57BL/6
MGI:106066  MP:0004003 abnormal vascular endothelial cell physiology PMID: 16299272 
Ptafrtm1Tksh Ptafrtm1Tksh/Ptafrtm1Tksh
involves: 129P2/OlaHsd * C57BL/6
MGI:106066  MP:0001876 decreased inflammatory response PMID: 14742561 
Ptafrtm1Tksh Ptafrtm1Tksh/Ptafrtm1Tksh
C57BL/6-Ptafr
MGI:106066  MP:0002411 decreased susceptibility to bacterial infection PMID: 14767826 
Ptafrtm1Tksh Ptafrtm1Tksh/Ptafrtm1Tksh
involves: 129P2/OlaHsd * C57BL/6
MGI:106066  MP:0005027 increased susceptibility to parasitic infection PMID: 14742561 
Ptafrtm1Tksh Ptafrtm1Tksh/Ptafrtm1Tksh
involves: 129P2/OlaHsd * C57BL/6
MGI:106066  MP:0005596 increased susceptibility to type I hypersensitivity reaction PMID: 9607919 
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  An Ala224 -> Asp substitution in the 3rd cytoplasmic loop of the PAF receptor has been found in Japanese subjects, with an estimated allele frequency of 7.8% among the Japanese population.
This polymorphism has been linked to an increased susceptibility to multiple sclerosis.
Amino acid change:  A224D
References:  22,51
General Comments
Transgenic mice overexpressing the guinea-pig PAF receptor have shown bronchial hyperreactivity to methacholine and increased mortality when exposed to bacterial endotoxin [32].

References

Show »

1. Albert DH, Conway RG, Magoc TJ, Tapang P, Rhein DA, Luo G, Holms JH, Davidsen SK, Summers JB, Carter GW. (1999) Properties of ABT-299, a prodrug of A-85783, a highly potent platelet activating factor receptor antagonist. J Pharmacol Exp Ther, 277: 1595-1606. [PMID:8667228]

2. Albert DH, Magoc TJ, Tapang P, Luo G, Morgan DW, Curtin M, Sheppard GS, Xu L, Heyman HR, Davidsen SK, Summers JB, Carter GW. (1997) Pharmacology of ABT-491, a highly potent platelet-activating factor receptor antagonist. Eur J Pharmacol, 325: 69-80. [PMID:9151941]

3. Aoki Y, Nakamura M, Kodama H, Matsumoto T, Shimizu T, Noma M. (1995) A radioreceptor binding assay for platelet-activating factor (PAF) using membranes from CHO cells expressing human PAF receptor. J Immunol Methods, 186: 225-231. [PMID:7594622]

4. Asano K, Taniguchi S, Nakao A, Watanabe T, Kurokawa K. (1996) Distribution of platelet activating factor receptor mRNA along the rat nephron segments. Biochem Biophys Res Commun, 225: 252-257. [PMID:8753768]

5. Bartemes KR, McKinney S, Gleich GJ, Kita H. (1999) Endogenous platelet-activating factor is critically involved in effector functions of eosinophils stimulated with IL-5 or IgG. J Immunol, 162: 2982-2989. [PMID:10072549]

6. Beaudeux JL, Said T, Ninio E, Ganné F, Soria J, Delattre J, Soria C, Legrand A, Peynet J. (2004) Activation of PAF receptor by oxidised LDL in human monocytes stimulates chemokine releases but not urokinase-type plasminogen activator expression. Clin. Chim. Acta, 344 (1-2): 163-71. [PMID:15149885]

7. Bito H, Honda Z, Nakamura M, Shimizu T. (1994) Cloning, expression and tissue distribution of rat platelet-activating-factor-receptor cDNA. Eur J Biochem, 221: 211-218. [PMID:8168510]

8. Brown SL, Jala VR, Raghuwanshi SK, Nasser MW, Haribabu B, Richardson RM. (2006) Activation and regulation of platelet-activating factor receptor: role of G(i) and G(q) in receptor-mediated chemotactic, cytotoxic, and cross-regulatory signals. J. Immunol., 177 (5): 3242-9. [PMID:16920964]

9. Bussolati B, Biancone L, Cassoni P, Russo S, Rola-Pleszczynski M, Montrucchio G, Camussi G. (2000) PAF produced by human breast cancer cells promotes migration and proliferation of tumor cells and neo-angiogenesis. Am J Pathol, 157: 1713-1725. [PMID:11073830]

10. Chase PB, Halonen M, Regan JW. (1993) Cloning of a human platelet-activating factor receptor gene: evidence for an intron in the 5'-untranslated region. Am J Respir Cell Mol Biol, 8: 240-244. [PMID:8383507]

11. Chen C, Magee JC, Marcheselli V, Hardy M, Bazan NG. (2001) Attenuated LTP in hippocampal dentate gyrus neurons of mice deficient in the PAF receptor. J Neurophysiol, 85: 384-390. [PMID:11152738]

12. Clark GD, Happel LT, Zorumski CF, Bazan NG. (1992) Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron, 9: 1211-1216. [PMID:1334422]

13. Curtin ML. (1998) Current status of platelet-activating factor antagonists. Expert Opinion on Therapeutic Patents, 8: 703-711.

14. de Oliveira SI, Fernandes PD, Amarante Mendes JG, Jancar S. (2006) Phagocytosis of apoptotic and necrotic thymocytes is inhibited by PAF-receptor antagonists and affects LPS-induced COX-2 expression in murine macrophages. Prostaglandins Other Lipid Mediat., 80 (1-2): 62-73. [PMID:16846787]

15. Del Maschio A, Evangelista V, Rajtar G, Chen ZM, Cerletti C, De Gaetano G. (1990) Platelet activation by polymorphonuclear leukocytes exposed to chemotactic agents. Am J Physiol, 258: 870-879. [PMID:2156456]

16. Deo DD, Bazan NG, Hunt JD. (2004) Activation of platelet-activating factor receptor-coupled G alpha q leads to stimulation of Src and focal adhesion kinase via two separate pathways in human umbilical vein endothelial cells. J Biol Chem, 279: 3497-3508. [PMID:14617636]

17. Desplat V, Besse A, Faucher JL, Praloran V, Denizot Y. (1999) Expression of platelet-activating factor receptor transcript-1 but not transcript-2 by human bone marrow cells. Stem Cells, 17: 121-124. [PMID:10195573]

18. Fernandes ES, Passos GF, Campos MM, Araujo JG, Pesquero JL, Avelllar MC, Teixeira MM, Calixto JB. (2003) Mechanisms underlying the modulatory action of platelet activating factor (PAF) on the upregulation of kinin B1 receptors in the rat paw. Br J Pharmacol, 139: 973-981. [PMID:12839871]

19. Fernández-Gallardo S, Ortega MP, Priego JG, de Casa-Juana MF, Sunkel C, Sánchez Crespo M. (1990) Pharmacological actions of PCA 4248, a new platelet-activating factor receptor antagonist: in vivo studies. J. Pharmacol. Exp. Ther., 255 (1): 34-9. [PMID:2170626]

20. Ferreira MA, Barcelos LS, Campos PP, Vasconcelos AC, Teixeira MM, Andrade SP. (2004) Sponge-induced angiogenesis and inflammation in PAF receptor-deficient mice (PAFR-KO). Br J Pharmacol, 141: 1185-1192. [PMID:15023865]

21. Flickinger BD, Olson MS. (1999) Localization of the platelet-activating factor receptor to rat pancreatic microvascular endothelial cells. Am J Pathol, 154: 1353-1358. [PMID:10329588]

22. Fukunaga K, Ishii S, Asano K, Yokomizo T, Shiomi T, Shimizu T, Yamaguchi K. (2001) Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation. J Biol Chem, 276: 43025-43030. [PMID:11560941]

23. Goldring WP, Alexander SP, Kendall DA, Pattenden G. (2005) Novel phomactin analogues as PAF receptor ligands. Bioorg Med Chem Lett, 15: 3263-3266. [PMID:15922596]

24. Handley DA, Van Valen RG, Melden MK, Houlihan WJ, Saunders RN. (1988) Biological effects of the orally active platelet activating factor receptor antagonist SDZ 64-412. J Pharmacol Exp Ther, 247: 617-623. [PMID:3183958]

25. Herbert JM, Laplace MC, Cailleau C, Maffrand JP. (1993) Effect of SR 27417 on the binding of [3H]PAF to rabbit and human platelets and human polymorphonuclear leukocytes. J Lipid Mediat, 7: 57-78. [PMID:8395255]

26. Heuer HO, Casals-Stenzel J, Muacevic G, Weber KH. (1990) Pharmacologic activity of bepafant (WEB 2170), a new and selective hetrazepinoic antagonist of platelet activating factor. J. Pharmacol. Exp. Ther., 255 (3): 962-8. [PMID:2262914]

27. Hikiji H, Ishii S, Shindou H, Takato T, Shimizu T. (2004) Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy. J Clin Invest, 114: 85-93. [PMID:15232615]

28. Hwang SB, Lam MH, Alberts AW, Bugianesi RL, Chabala JC, Ponpipom MM. (1988) Biochemical and pharmacological characterization of L-659,989: an extremely potent, selective and competitive receptor antagonist of platelet-activating factor. J. Pharmacol. Exp. Ther., 246 (2): 534-41. [PMID:2841449]

29. Ishii S, Kuwaki T, Nagase T, Maki K, Tashiro F, Sunaga S, Cao WH, Kume K, Fukuchi Y, Ikuta K, Miyazaki J, Kumada M, Shimizu T. (1998) Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor. J Exp Med, 187: 1779-1788. [PMID:9607919]

30. Ishii S, Matsuda Y, Nakamura M, Waga I, Kume K, Izumi T, Shimizu T. (1996) A murine platelet-activating factor receptor gene: cloning, chromosomal localization and up-regulation of expression by lipopolysaccharide in peritoneal resident macrophages. Biochem J, 314: 671-678. [PMID:8670084]

31. Ishii S, Nagase T, Shindou H, Takizawa H, Ouchi Y, Shimizu T. (2004) Platelet-activating factor receptor develops airway hyperresponsiveness independently of airway inflammation in a murine asthma model. J Immunol, 172: 7095-7102. [PMID:15153532]

32. Ishii S, Nagase T, Tashiro F, Ikuta K, Sato S, Waga I, Kume K, Miyazaki J, Shimizu T. (1997) Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor. Embo J, 16: 133-142. [PMID:9009274]

33. Ivanov AI, Patel S, Kulchitsky VA, Romanovsky AA. (2003) Platelet-activating factor: a previously unrecognized mediator of fever. J Physiol, 553: 221-228. [PMID:14565987]

34. Kamata K, Numazawa T, Kasuya Y. (1996) Characteristics of vasodilatation induced by acetylcholine and platelet-activating factor in the rat mesenteric arterial bed. Eur J Pharmacol, 298: 129-136. [PMID:8867099]

35. Kaminski JJ, Carruthers NI, Wong SC, Chan TM, Billah MM, Tozzi S, McPhail AT. (1999) Conformational considerations in the design of dual antagonists of platelet-activating factor (PAF) and histamine. Bioorg Med Chem, 7: 1413-1423. [PMID:10465415]

36. Kunz D, Gerard NP, Gerard C. (1992) The human leukocyte platelet-activating factor receptor. cDNA cloning, cell surface expression, and construction of a novel epitope-bearing analog. J Biol Chem, 267: 9101-9106. [PMID:1374385]

37. Lukashova V, Asselin C, Krolewski JJ, Rola-Pleszczynski M, Stanková J. (2001) G-protein-independent activation of Tyk2 by the platelet-activating factor receptor. J. Biol. Chem., 276 (26): 24113-21. [PMID:11309383]

38. Lukashova V, Chen Z, Duhé RJ, Rola-Pleszczynski M, Stanková J. (2003) Janus kinase 2 activation by the platelet-activating factor receptor (PAFR): roles of Tyk2 and PAFR C terminus. J. Immunol., 171 (7): 3794-800. [PMID:14500680]

39. Ma X, Ottino P, Bazan HE, Bazan NG. (2004) Platelet-activating factor (PAF) induces corneal neovascularization and upregulates VEGF expression in endothelial cells. Invest Ophthalmol Vis Sci, 45: 2915-2921. [PMID:15326102]

40. Marathe GK, Davies SS, Harrison KA, Silva AR, Murphy RC, Castro-Faria-Neto H, Prescott SM, Zimmerman GA, McIntyre TM. (1999) Inflammatory platelet-activating factor-like phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines. J Biol Chem, 274: 28395-28404. [PMID:10497200]

41. Marathe GK, Harrison KA, Murphy RC, Prescott SM, Zimmerman GA, McIntyre TM. (2000) Bioactive phospholipid oxidation products. Free Radic Biol Med, 28: 1762-1770. [PMID:10946218]

42. Marquis O, Robaut C, Cavero I. (1988) [3H]52770 RP, a platelet-activating factor receptor antagonist, and tritiated platelet-activating factor label a common specific binding site in human polymorphonuclear leukocytes. J Pharmacol Exp Ther, 244: 709-715. [PMID:2831350]

43. McIntyre TM. (2012) Bioactive oxidatively truncated phospholipids in inflammation and apoptosis: Formation, targets, and inactivation. Biochim. Biophys. Acta, 1818 (10): 2456-64. [PMID:22445850]

44. Mori M, Aihara M, Kume K, Hamanoue M, Kohsaka S, Shimizu T. (1996) Predominant expression of platelet-activating factor receptor in the rat brain microglia. J Neurosci, 16: 3590-3600. [PMID:8642404]

45. Morita K, Morioka N, Abdin J, Kitayama S, Nakata Y, Dohi T. (2004) Development of tactile allodynia and thermal hyperalgesia by intrathecally administered platelet-activating factor in mice. Pain, 111: 351-359. [PMID:15363879]

46. Nagase T, Ishii S, Katayama H, Fukuchi Y, Ouchi Y, Shimizu T. (1997) Airway responsiveness in transgenic mice overexpressing platelet-activating factor receptor. Roles of thromboxanes and leukotrienes. Am J Respir Crit Care Med, 156: 1621-1627. [PMID:9372685]

47. Nagase T, Ishii S, Kume K, Uozumi N, Izumi T, Ouchi Y, Shimizu T. (1999) Platelet-activating factor mediates acid-induced lung injury in genetically engineered mice. J Clin Invest, 104: 1071-1076. [PMID:10525045]

48. Nagase T, Ishii S, Shindou H, Ouchi Y, Shimizu T. (2002) Airway hyperresponsiveness in transgenic mice overexpressing platelet activating factor receptor is mediated by an atropine-sensitive pathway. Am J Respir Crit Care Med, 165: 200-205. [PMID:11790655]

49. Nakamura M, Honda Z, Izumi T, Sakanaka C, Mutoh H, Minami M, Bito H, Seyama Y, Matsumoto T, Noma M et al.. (1991) Molecular cloning and expression of platelet-activating factor receptor from human leukocytes. J. Biol. Chem., 266 (30): 20400-5. [PMID:1657923]

50. Negrao-Correa D, Souza DG, Pinho V, Barsante MM, Souza AL, Teixeira MM. (2004) Platelet-activating factor receptor deficiency delays elimination of adult worms but reduces fecundity in Strongyloides venezuelensis-infected mice. Infect Immun, 72: 1135-1142. [PMID:14742561]

51. Osoegawa M, Miyagishi R, Ochi H, Nakamura I, Niino M, Kikuchi S, Murai H, Fukazawa T, Minohara M, Tashiro K, Kira J. (2005) Platelet-activating factor receptor gene polymorphism in Japanese patients with multiple sclerosis. J Neuroimmunol, 161: 195-198. [PMID:15748960]

52. Parent JL, Gouill CL, Escher E, Rola-Pleszczynski M, Stakova J. (1996) Identification of transmembrane domain residues determinant in the structure-function relationship of the human platelet-activating factor receptor by site-directed mutagenesis. J Biol Chem, 271: 23298-23303. [PMID:8798529]

53. Perry SW, Hamilton JA, Tjoelker LW, Dbaibo G, Dzenko KA, Epstein LG, Hannun Y, Whittaker JS, Dewhurst S, Gelbard HA. (1998) Platelet-activating factor receptor activation. An initiator step in HIV-1 neuropathogenesis. J Biol Chem, 273: 17660-17664. [PMID:9651362]

54. Reinhardt JC, Cui X, Roudebush WE. (1999) Immunofluorescent evidence of the platelet-activating factor receptor on human spermatozoa. Fertil Steril, 71: 941-942. [PMID:10231061]

55. Rijneveld AW, Weijer S, Florquin S, Speelman P, Shimizu T, Ishii S, van der Poll T. (2004) Improved host defense against pneumococcal pneumonia in platelet-activating factor receptor-deficient mice. J Infect Dis, 189: 711-716. [PMID:14767826]

56. Rios FJ, Koga MM, Ferracini M, Jancar S. (2012) Co-stimulation of PAFR and CD36 is required for oxLDL-induced human macrophages activation. PLoS ONE, 7 (5): e36632. [PMID:22570732]

57. Row BW, Kheirandish L, Li RC, Guo SZ, Brittian KR, Hardy M, Bazan NG, Gozal D. (2004) Platelet-activating factor receptor-deficient mice are protected from experimental sleep apnea-induced learning deficits. J Neurochem, 89: 189-196. [PMID:15030403]

58. Sahu RP, Turner MJ, DaSilva SC, Rashid BM, Ocana JA, Perkins SM, Konger RL, Touloukian CE, Kaplan MH, Travers JB. (2012) The environmental stressor ultraviolet B radiation inhibits murine antitumor immunity through its ability to generate platelet-activating factor agonists. Carcinogenesis, 33 (7): 1360-7. [PMID:22542595]

59. Sato S, Kume K, Ito C, Ishii S, Shimizu T. (1999) Accelerated proliferation of epidermal keratinocytes by the transgenic expression of the platelet-activating factor receptor. Arch Dermatol Res, 291: 614-621. [PMID:10638335]

60. Seyfried CE, Schweickart VL, Godiska R, Gray PW. (1992) The human platelet-activating factor receptor gene (PTAFR) contains no introns and maps to chromosome 1. Genomics, 13: 832-834. [PMID:1322356]

61. Shah BH, Rasheed H, Rahman IH, Shariff AH, Khan FL, Rahman HB, Hanif S, Saeed SA. (2001) Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine. Exp Mol Med, 33: 226-233. [PMID:11795484]

62. Smiley PL, Stremler KE, Prescott SM, Zimmerman GA, McIntyre TM. (1991) Oxidatively fragmented phosphatidylcholines activate human neutrophils through the receptor for platelet-activating factor. J Biol Chem, 266: 11104-11110. [PMID:1645725]

63. Stromgaard K, Saito DR, Shindou H, Ishii S, Shimizu T, Nakanishi K. (2002) Ginkgolide derivatives for photolabeling studies: preparation and pharmacological evaluation. J Med Chem, 45: 4038-4046. [PMID:12190325]

64. Sugimoto T, Tsuchimochi H, McGregor CG, Mutoh H, Shimizu T, Kurachi Y. (1992) Molecular cloning and characterization of the platelet-activating factor receptor gene expressed in the human heart. Biochem Biophys Res Commun, 189: 617-624. [PMID:1281995]

65. Summers JB, Albert DH. (1995) Platelet activating factor antagonists. Adv Pharmacol, 32: 67-168. [PMID:7748804]

66. Svetlov S, Nigam S. (1993) Evidence for the presence of specific high affinity cytosolic binding sites for platelet-activating factor in human neutrophils. Biochem Biophys Res Commun, 190: 162-166. [PMID:8380690]

67. Talvani A, Santana G, Barcelos LS, Ishii S, Shimizu T, Romanha AJ, Silva JS, Soares MB, Teixeira MM. (2003) Experimental Trypanosoma cruzi infection in platelet-activating factor receptor-deficient mice. Microbes Infect, 5: 789-796. [PMID:12850205]

68. Terashita Z, Imura Y, Nishikawa K. (1985) Inhibition by CV-3988 of the binding of [3H]-platelet activating factor (PAF) to the platelet. Biochem. Pharmacol., 34 (9): 1491-5. [PMID:2986648]

69. Tokuoka SM, Ishii S, Kawamura N, Satoh M, Shimada A, Sasaki S, Hirotsune S, Wynshaw-Boris A, Shimizu T. (2003) Involvement of platelet-activating factor and LIS1 in neuronal migration. Eur J Neurosci, 18: 563-570. [PMID:12911752]

70. Velasquez LA, Maisey K, Fernandez R, Valdes D, Cardenas H, Imarai M, Delgado J, Aguilera J, Croxatto HB. (2001) PAF receptor and PAF acetylhydrolase expression in the endosalpinx of the human Fallopian tube: possible role of embryo-derived PAF in the control of embryo transport to the uterus. Hum Reprod, 16: 1583-1587. [PMID:11473946]

71. Vogensen SB, Stromgaard K, Shindou H, Jaracz S, Suehiro M, Ishii S, Shimizu T, Nakanishi K. (2003) Preparation of 7-substituted ginkgolide derivatives: potent platelet activating factor (PAF) receptor antagonists. J Med Chem, 46: 601-608. [PMID:12570381]

Contributors

Show »

How to cite this page

Rebecca Hills, Mark Whittaker.
Platelet-activating factor receptor: PAF receptor. Last modified on 20/02/2018. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=334.