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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 478

Nomenclature: P2X1

Family: P2X receptors

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 399 17p13.2 P2RX1 purinergic receptor P2X 1 52
Mouse 2 399 11 45.09 cM P2rx1 purinergic receptor P2X, ligand-gated ion channel, 1 29
Rat 2 399 10q24 P2rx1 purinergic receptor P2X 1 51
Previous and Unofficial Names Click here for help
P2XR1 | P2X purinoceptor 1 | P2X1 receptor | Pdcd3 | purinergic receptor P2X, ligand gated ion channel, 1 | purinergic receptor P2X
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands Click here for help

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ATP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 7.3 pEC50 17
pEC50 7.3 (EC50 5.6x10-8 M) [17]
BzATP Small molecule or natural product Click here for species-specific activity table Hs Full agonist - -
αβ-meATP Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist - -
L-βγ-meATP Small molecule or natural product Ligand has a PDB structure Hs Full agonist - -
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
TNP-ATP Small molecule or natural product Click here for species-specific activity table Hs Antagonist ~8.9 pIC50 58
pIC50 ~8.9 (IC50 ~1.3x10-9 M) [58]
Ip5I Small molecule or natural product Hs Antagonist ~8.5 pIC50 23
pIC50 ~8.5 (IC50 ~3.2x10-9 M) [23]
MRS2159 Small molecule or natural product Rn Antagonist ~8.0 pIC50 22
pIC50 ~8.0 (IC50 ~1x10-8 M) [22]
NF279 Small molecule or natural product Hs Antagonist 7.3 – 7.7 pIC50 24,41
pIC50 7.7 (IC50 1.99x10-8 M) [41]
pIC50 7.3 (IC50 5x10-8 M) [24]
NF023 Small molecule or natural product Hs Antagonist ~6.7 pIC50 48
pIC50 ~6.7 (IC50 ~2x10-7 M) [48]
NF449 Small molecule or natural product Hs Antagonist ~6.3 pIC50 20
pIC50 ~6.3 (IC50 ~5x10-7 M) [20]
suramin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 6.0 pIC50 17
pIC50 6.0 (IC50 1x10-6 M) [17]
View species-specific antagonist tables
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
MRS 2219 Small molecule or natural product Hs Positive - - - no 18
Not voltage dependent
Immunopharmacology Comments
Functional P2X1 receptors are expressed by healthy human eosinophils [64]. In these cells P2X1 receptor activation is involved in αMβ2 integrin-dependent adhesion. Responses of eosinophils from asthmatic patients are reduced, potentially by increased extracellular nucleotide concentration as detected in bronchoalveolar lavage fluids from patients with airway inflammations [10,15,30,42].
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
References:  64
Immuno Cell Type:  B cells
Comment:  Human B cells express all P2 receptor subtypes.
References:  40
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  P2XR1 and P2XR3 are expressed by mast cells.
References:  5,50
Immuno Cell Type:  T cells
Comment:  T cells express P2X receptors 1, 4 and 5. ATP-induced activation of these receptors in T cells is associated with proliferation, cytokine production and thymocyte apoptosis.
References:  5,50
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cellular signalling
Tissue Distribution Click here for help
Heart tissue.
Expression level:  Medium
Species:  Human
Technique:  Immunohistochemistry, Western blotting, RT-PCR
References:  3,14,19
Smooth muscle; bladder, vas deferens, arteries
Expression level:  High
Species:  Human
Technique:  Immunohistochemistry, Northern blot, RT-PCR, Western Blot
References:  2,4,31,52,61
Blood cells; platelets, mast cells, lymphocytes
Expression level:  High
Species:  Human
Technique:  Immunohistochemistry, Western blot
References:  44,47,56,63
Macrophages, neutrophils, megakaryocytes/platelts, pancreatic beta cells
Expression level:  Medium
Species:  Mouse
Technique:  Immunohistochemistry, Knockouts
References:  27,45-46,57
Astrocytes, cerebellar granule neurons
Expression level:  Medium
Species:  Mouse
Technique:  RT-PCR
References:  25,49
Smooth muscle; vas deferens, bladder, arteries
Expression level:  High
Species:  Mouse
Technique:  Immunohistochemistry
References:  34,53-55
Smooth muscle; vas deferens, bladder, arteries, portal vein, myometrium
Expression level:  High
Species:  Rat
Technique:  Immunohistochemistry and in situ hybridisation.
References:  6-7,21,28,33,35,51,59
Spinal cord, superior cervical ganalion, sensory ganglia, hippocampal neurons
Expression level:  Medium
Species:  Rat
Technique:  in situ hybridisation, RT-PCR
References:  6-7,21,28,33,35,43
Tissue Distribution Comments
The commonly used anti-P2X1 receptor antibody may not be selective in neuronal tissues [1] and so studies using this approach have not been included.
Physiological Functions Click here for help
P2X1 expressed on polymorphonuclear neutrophils and platelets is required for thrombosis in mice.
Species:  Mouse
References:  8
Exposure to the endotoxin LPS induces ATP signalling via P2X1 that causes inhibition of neutrophil chemotaxis in vitro.
Species:  Human
Tissue:  Primary human neutrophils, differentiated HL-60 cells.
References:  62
Physiological Consequences of Altering Gene Expression Click here for help
Male infertility
Species:  Mouse
Tissue:  Vas deferens
Technique:  Knock out
References:  34
Reduced nerve evoked bladder contraction
Species:  Mouse
Tissue:  Urinary (bladder)
Technique:  Knock out
References:  53
Reduced nerve evoked artery contraction
Species:  Mouse
Tissue:  Mesenteric artery
Technique:  knock out
References:  26,55
Reduced kidney autoregulation of blood flow
Species:  Mouse
Tissue:  Kidney arterioles
Technique:  knock out
References:  16
Decreased mortality in thromboembolism models
Species:  Mouse
Tissue:  Platelets
Technique:  Knock out
References:  9,13
Increased mortality in thromboembolism models
Species:  Mouse
Tissue:  Platelets
Technique:  megakaryocyte specific over-expression
References:  38
Reduced ATP evoked P2X receptor currents in macrophages
Species:  Mouse
Tissue:  Macrophages
Technique:  Knock out
References:  46
P2X1 null mice show a markedly diminished pathological response to LPS challenge, likely caused by reduce chemotaxis of neutrophils from venules in to tissues.
Species:  Mouse
References:  27,32
Gene Expression and Pathophysiology Click here for help
Tissue or cell type:  Heart
Pathophysiology:  Congestive heart failure
Species:  Human
Technique:  RT-PCR
References:  14
Tissue or cell type:  Heart-atria
Pathophysiology:  Dilated cardiomyopathy
Species:  Human
Technique:  Western blot
References:  3
Tissue or cell type:  Shear stress
Pathophysiology:  Umbilical vein smooth muscle
Species:  Human
Technique:  RT-PCR, Western blot, immunohistochemistry
References:  60
Tissue or cell type:  Urinary-bladder
Pathophysiology:  Outlet obstruction
Species:  Human
Technique:  RT-PCR
References:  36
Gene Expression and Pathophysiology Comments
Eosinophils from asthmatic patients exhibit impaired P2X1 receptor-mediated adhesion [64].
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  P2X1del (deletion:176-192)
References:  11
Type:  Splice variant
Species:  Human
Description:  P2X1del (deletion:346-379)
References:  12
Type:  Splice variant
Species:  Human
Description:  P2X1delL (deletion:353)
References:  39
Type:  Splice variant
Species:  Rat
Description:  P2X1a receptor isoform (deletion:175-201)
Amino acids:  372
Nucleotide accession: 
Protein accession: 
References:  37
General Comments
An alternatively spliced variant of the rat P2X1 subunit, provisionally termed p2X1a which lacks function as a homomer has been described [37]. An inactive, naturally occurring human mutant dominant negative P2X receptor has also been reported [39].


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1. Ashour F, Atterbury-Thomas M, Deuchars J, Evans RJ. (2006) An evaluation of antibody detection of the P2X1 receptor subunit in the CNS of wild type and P2X1-knockout mice. Neurosci Lett, 397 (1-2): 120-5. [PMID:16384637]

2. Banks FC, Knight GE, Calvert RC, Thompson CS, Morgan RJ, Burnstock G. (2006) The purinergic component of human vas deferens contraction. Fertil Steril, 85 (4): 932-9. [PMID:16580377]

3. Berry DA, Barden JA, Balcar VJ, Keogh A, dos Remedios CG. (1999) Increase in expression of P2X1 receptors in the atria of patients suffering from dilated cardiomyopathy. Electrophoresis, 20 (10): 2059-64. [PMID:10451115]

4. Bo X, Karoon P, Nori SL, Bardini M, Burnstock G. (1998) P2X purinoceptors in postmortem human cerebral arteries. J Cardiovasc Pharmacol, 31 (5): 794-9. [PMID:9593081]

5. Cekic C, Linden J. (2016) Purinergic regulation of the immune system. Nat Rev Immunol, 16 (3): 177-92. [PMID:26922909]

6. Chan CM, Unwin RJ, Bardini M, Oglesby IB, Ford AP, Townsend-Nicholson A, Burnstock G. (1998) Localization of P2X1 purinoceptors by autoradiography and immunohistochemistry in rat kidneys. Am J Physiol, 274 (4 Pt 2): F799-804. [PMID:9575906]

7. Collo G, North RA, Kawashima E, Merlo-Pich E, Neidhart S, Surprenant A, Buell G. (1996) Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. J Neurosci, 16 (8): 2495-507. [PMID:8786426]

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9. Erhardt JA, Toomey JR, Douglas SA, Johns DG. (2006) P2X1 stimulation promotes thrombin receptor-mediated platelet aggregation. J Thromb Haemost, 4 (4): 882-90. [PMID:16634759]

10. Esther Jr CR, Alexis NE, Clas ML, Lazarowski ER, Donaldson SH, Ribeiro CM, Moore CG, Davis SD, Boucher RC. (2008) Extracellular purines are biomarkers of neutrophilic airway inflammation. Eur Respir J, 31 (5): 949-56. [PMID:18256064]

11. Greco NJ, Tonon G, Chen W, Luo X, Dalal R, Jamieson GA. (2001) Novel structurally altered P(2X1) receptor is preferentially activated by adenosine diphosphate in platelets and megakaryocytic cells. Blood, 98 (1): 100-7. [PMID:11418468]

12. Hardy LA, Harvey IJ, Chambers P, Gillespie JI. (2000) A putative alternatively spliced variant of the P2X(1) purinoreceptor in human bladder. Exp Physiol, 85 (4): 461-3. [PMID:10918085]

13. Hechler B, Lenain N, Marchese P, Vial C, Heim V, Freund M, Cazenave JP, Cattaneo M, Ruggeri ZM, Evans R et al.. (2003) A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo. J Exp Med, 198 (4): 661-7. [PMID:12913094]

14. Hou M, Malmsjö M, Möller S, Pantev E, Bergdahl A, Zhao XH, Sun XY, Hedner T, Edvinsson L, Erlinge D. (1999) Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure. Life Sci, 65 (11): 1195-206. [PMID:10503935]

15. Idzko M, Hammad H, van Nimwegen M, Kool M, Willart MA, Muskens F, Hoogsteden HC, Luttmann W, Ferrari D, Di Virgilio F et al.. (2007) Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat Med, 13 (8): 913-9. [PMID:17632526]

16. Inscho EW, Cook AK, Imig JD, Vial C, Evans RJ. (2003) Physiological role for P2X1 receptors in renal microvascular autoregulatory behavior. J Clin Invest, 112 (12): 1895-905. [PMID:14679185]

17. Jacobson KA, Jarvis MF, Williams M. (2002) Purine and pyrimidine (P2) receptors as drug targets. J Med Chem, 45 (19): 4057-93. [PMID:12213051]

18. Jacobson KA, Kim YC, Wildman SS, Mohanram A, Harden TK, Boyer JL, King BF, Burnstock G. (1998) A pyridoxine cyclic phosphate and its 6-azoaryl derivative selectively potentiate and antagonize activation of P2X1 receptors. J Med Chem, 41 (13): 2201-6. [PMID:9632352]

19. Jiang L, Bardini M, Keogh A, dos Remedios CG, Burnstock G. (2005) P2X1 receptors are closely associated with connexin 43 in human ventricular myocardium. Int J Cardiol, 98 (2): 291-7. [PMID:15686781]

20. Kassack MU, Braun K, Ganso M, Ullmann H, Nickel P, Böing B, Müller G, Lambrecht G. (2004) Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist. Eur J Med Chem, 39 (4): 345-57. [PMID:15072843]

21. Khanam T, Burnstock G. (2007) Changes in expression of P2X1 receptors and connexin 43 in the rat myometrium during pregnancy. Fertil Steril, 88 (4 Suppl): 1174-9. [PMID:17561003]

22. Kim YC, Brown SG, Harden TK, Boyer JL, Dubyak G, King BF, Burnstock G, Jacobson KA. (2001) Structure-activity relationships of pyridoxal phosphate derivatives as potent and selective antagonists of P2X1 receptors. J Med Chem, 44 (3): 340-9. [PMID:11462975]

23. King BF, Liu M, Pintor J, Gualix J, Miras-Portugal MT, Burnstock G. (1999) Diinosine pentaphosphate (IP5I) is a potent antagonist at recombinant rat P2X1 receptors. Br J Pharmacol, 128 (5): 981-8. [PMID:10556935]

24. Klapperstück M, Büttner C, Nickel P, Schmalzing G, Lambrecht G, Markwardt F. (2000) Antagonism by the suramin analogue NF279 on human P2X(1) and P2X(7) receptors. Eur J Pharmacol, 387 (3): 245-52. [PMID:10650169]

25. Lalo U, Pankratov Y, Wichert SP, Rossner MJ, North RA, Kirchhoff F, Verkhratsky A. (2008) P2X1 and P2X5 subunits form the functional P2X receptor in mouse cortical astrocytes. J Neurosci, 28 (21): 5473-80. [PMID:18495881]

26. Lamont C, Vainorius E, Wier WG. (2003) Purinergic and adrenergic Ca2+ transients during neurogenic contractions of rat mesenteric small arteries. J Physiol (Lond.), 549 (Pt 3): 801-8. [PMID:12740429]

27. Lecut C, Frederix K, Johnson DM, Deroanne C, Thiry M, Faccinetto C, Marée R, Evans RJ, Volders PG, Bours V et al.. (2009) P2X1 ion channels promote neutrophil chemotaxis through Rho kinase activation. J Immunol, 183 (4): 2801-9. [PMID:19635923]

28. Lewis CJ, Evans RJ. (2001) P2X receptor immunoreactivity in different arteries from the femoral, pulmonary, cerebral, coronary and renal circulations. J Vasc Res, 38 (4): 332-40. [PMID:11455204]

29. Liang SX, Jenkins NA, Gilbert DJ, Copeland NG, Phillips WD. (2001) Structure and chromosome location of the mouse P2X(1) purinoceptor gene (P2rx1). Cytogenet Cell Genet, 92 (3-4): 333-6. [PMID:11435708]

30. Lommatzsch M, Cicko S, Müller T, Lucattelli M, Bratke K, Stoll P, Grimm M, Dürk T, Zissel G, Ferrari D et al.. (2010) Extracellular adenosine triphosphate and chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 181 (9): 928-34. [PMID:20093639]

31. Longhurst PA, Schwegel T, Folander K, Swanson R. (1996) The human P2x1 receptor: molecular cloning, tissue distribution, and localization to chromosome 17. Biochim Biophys Acta, 1308 (3): 185-8. [PMID:8809107]

32. Maître B, Magnenat S, Heim V, Ravanat C, Evans RJ, de la Salle H, Gachet C, Hechler B. (2015) The P2X1 receptor is required for neutrophil extravasation during lipopolysaccharide-induced lethal endotoxemia in mice. J Immunol, 194 (2): 739-49. [PMID:25480563]

33. Mironneau J, Coussin F, Morel JL, Barbot C, Jeyakumar LH, Fleischer S, Mironneau C. (2001) Calcium signalling through nucleotide receptor P2X1 in rat portal vein myocytes. J Physiol (Lond.), 536 (Pt 2): 339-50. [PMID:11600670]

34. Mulryan K, Gitterman DP, Lewis CJ, Vial C, Leckie BJ, Cobb AL, Brown JE, Conley EC, Buell G, Pritchard CA et al.. (2000) Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors. Nature, 403 (6765): 86-9. [PMID:10638758]

35. Nori S, Fumagalli L, Bo X, Bogdanov Y, Burnstock G. (1998) Coexpression of mRNAs for P2X1, P2X2 and P2X4 receptors in rat vascular smooth muscle: an in situ hybridization and RT-PCR study. J Vasc Res, 35 (3): 179-85. [PMID:9647332]

36. O'Reilly BA, Kosaka AH, Chang TK, Ford AP, Popert R, McMahon SB. (2001) A quantitative analysis of purinoceptor expression in the bladders of patients with symptomatic outlet obstruction. BJU Int, 87 (7): 617-22. [PMID:11350400]

37. Ohkubo T, Yamazaki J, Nakashima Y, Kitamura K. (2000) Presence and possible role of the spliced isoform of the P2X1 receptor in rat vascular smooth muscle cells. Pflugers Arch, 441 (1): 57-64. [PMID:11205062]

38. Oury C, Kuijpers MJ, Toth-Zsamboki E, Bonnefoy A, Danloy S, Vreys I, Feijge MA, De Vos R, Vermylen J, Heemskerk JW et al.. (2003) Overexpression of the platelet P2X1 ion channel in transgenic mice generates a novel prothrombotic phenotype. Blood, 101 (10): 3969-76. [PMID:12521992]

39. Oury C, Toth-Zsamboki E, Van Geet C, Thys C, Wei L, Nilius B, Vermylen J, Hoylaerts MF. (2000) A natural dominant negative P2X1 receptor due to deletion of a single amino acid residue. J Biol Chem, 275 (30): 22611-4. [PMID:10816552]

40. Przybyła T, Sakowicz-Burkiewicz M, Pawełczyk T. (2018) Purinergic signaling in B cells. Acta Biochim Pol, 65 (1): 1-7. [PMID:29360885]

41. Rettinger J, Schmalzing G, Damer S, Müller G, Nickel P, Lambrecht G. (2000) The suramin analogue NF279 is a novel and potent antagonist selective for the P2X(1) receptor. Neuropharmacology, 39 (11): 2044-53. [PMID:10963748]

42. Riteau N, Gasse P, Fauconnier L, Gombault A, Couegnat M, Fick L, Kanellopoulos J, Quesniaux VF, Marchand-Adam S, Crestani B et al.. (2010) Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med, 182 (6): 774-83. [PMID:20522787]

43. Rodrigues RJ, Almeida T, Richardson PJ, Oliveira CR, Cunha RA. (2005) Dual presynaptic control by ATP of glutamate release via facilitatory P2X1, P2X2/3, and P2X3 and inhibitory P2Y1, P2Y2, and/or P2Y4 receptors in the rat hippocampus. J Neurosci, 25 (27): 6286-95. [PMID:16000618]

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48. Soto F, Lambrecht G, Nickel P, Stühmer W, Busch AE. (1999) Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors. Neuropharmacology, 38 (1): 141-9. [PMID:10193905]

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53. Vial C, Evans RJ. (2000) P2X receptor expression in mouse urinary bladder and the requirement of P2X(1) receptors for functional P2X receptor responses in the mouse urinary bladder smooth muscle. Br J Pharmacol, 131 (7): 1489-95. [PMID:11090125]

54. Vial C, Evans RJ. (2001) Smooth muscle does not have a common P2x receptor phenotype: expression, ontogeny and function of P2x1 receptors in mouse ileum, bladder and reproductive systems. Auton Neurosci, 92 (1-2): 56-64. [PMID:11570704]

55. Vial C, Evans RJ. (2002) P2X(1) receptor-deficient mice establish the native P2X receptor and a P2Y6-like receptor in arteries. Mol Pharmacol, 62 (6): 1438-45. [PMID:12435812]

56. Vial C, Hechler B, Léon C, Cazenave JP, Gachet C. (1997) Presence of P2X1 purinoceptors in human platelets and megakaryoblastic cell lines. Thromb Haemost, 78 (6): 1500-4. [PMID:9423802]

57. Vial C, Rolf MG, Mahaut-Smith MP, Evans RJ. (2002) A study of P2X1 receptor function in murine megakaryocytes and human platelets reveals synergy with P2Y receptors. Br J Pharmacol, 135 (2): 363-72. [PMID:11815371]

58. Virginio C, Robertson G, Surprenant A, North RA. (1998) Trinitrophenyl-substituted nucleotides are potent antagonists selective for P2X1, P2X3, and heteromeric P2X2/3 receptors. Mol Pharmacol, 53 (6): 969-73. [PMID:9614197]

59. Vulchanova L, Arvidsson U, Riedl M, Wang J, Buell G, Surprenant A, North RA, Elde R. (1996) Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry. Proc Natl Acad Sci USA, 93 (15): 8063-7. [PMID:8755603]

60. Wang L, Andersson M, Karlsson L, Watson MA, Cousens DJ, Jern S, Erlinge D. (2003) Increased mitogenic and decreased contractile P2 receptors in smooth muscle cells by shear stress in human vessels with intact endothelium. Arterioscler Thromb Vasc Biol, 23 (8): 1370-6. [PMID:12791671]

61. Wang L, Karlsson L, Moses S, Hultgårdh-Nilsson A, Andersson M, Borna C, Gudbjartsson T, Jern S, Erlinge D. (2002) P2 receptor expression profiles in human vascular smooth muscle and endothelial cells. J Cardiovasc Pharmacol, 40 (6): 841-53. [PMID:12451317]

62. Wang X, Qin W, Xu X, Xiong Y, Zhang Y, Zhang H, Sun B. (2017) Endotoxin-induced autocrine ATP signaling inhibits neutrophil chemotaxis through enhancing myosin light chain phosphorylation. Proc Natl Acad Sci USA, 114 (17): 4483-4488. [PMID:28396412]

63. Wareham K, Vial C, Wykes RC, Bradding P, Seward EP. (2009) Functional evidence for the expression of P2X1, P2X4 and P2X7 receptors in human lung mast cells. Br J Pharmacol, 157 (7): 1215-24. [PMID:19552691]

64. Wright A, Mahaut-Smith M, Symon F, Sylvius N, Ran S, Bafadhel M, Muessel M, Bradding P, Wardlaw A, Vial C. (2016) Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients. J Immunol, 196 (12): 4877-84. [PMID:27183585]


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