Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport

Scientific Reports

Volumn 8, Issue 1, 2018, Pages

  Roweth, Harvey G ^a   Yan, Ruoling ^a   Bedwani, Nader H ^a   Chauhan, Alisha ^a   Fowler, Nicole ^a   Watson, Alice H ^a   Malcor, Jean Daniel ^a   Sage, Stewart O ^a   Jarvis, Gavin E ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CITALOPRAM; SEROTONIN; SEROTONIN TRANSPORTER; SEROTONIN UPTAKE INHIBITOR; SLC6A4 PROTEIN, HUMAN; THROMBOXANE A2;

ANIMAL; BIOSYNTHESIS; DRUG EFFECT; GENETICS; HUMAN; LEPORIDAE; METABOLISM; MOUSE; NORMAL HUMAN; PATHOLOGY; PHOSPHORYLATION; SIGNAL TRANSDUCTION; THROMBOCYTE; THROMBOCYTE AGGREGATION;

ANIMALS; BLOOD PLATELETS; CITALOPRAM; HEALTHY VOLUNTEERS; HUMANS; MICE; PHOSPHORYLATION; PLATELET AGGREGATION; RABBITS; SEROTONIN; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SEROTONIN UPTAKE INHIBITORS; SIGNAL TRANSDUCTION; THROMBOXANE A2;

EID: 85042539153     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-018-21348-3     Document Type: Article

References (65)

1. Cipriani, A. et al. Citalopram versus other anti-depressive agents for depression. Cochrane Database Syst Rev 7, 1-172 (2012).
2. Maurer-Spurej, E., Pittendreigh, C. & Solomons, K. The influence of selective serotonin reuptake inhibitors on serotonin metabolism in human platelets. Thromb Haemost 91, 119-128 (2004).
3. Jonnakuty, C. & Gragnoli, C. What do we know about serotonin? J Cell Physiol 217, 301-306 (2008).
4. Brenner, B. et al. Plasma serotonin levels and the platelet serotonin transporter. J Neurochem 102, 206-215 (2007).
5. Lin, O. A., Karim, Z. A., Vemana, H. P., Espinosa, E. V. P. & Khasawneh, F. T. The antidepressant 5-HT2A receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function. PLoS One 9, e87026 (2014).
6. Nagatomo, T., Rashid, M., Abul Muntasir, H. & Komiyama, T. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system. Pharmacol Ther 104, 59-81 (2004).
7. Rapport, M., Green, A. & Page, H. Partial purification of the vasoconstrictor in beef serum. J Biol Chem 174, 735-741 (1948).
8. Sauer, W. H., Berlin, J. A. & Kimmel, S. E. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 104, 1894-1898 (2001).
9. de Abajo, F. J., García Rodríguez, L. A. & Montero, D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: Population based case-control study. Br Med J 319, 1106-1109 (1999).
10. Hackam, D. G. & Mrkobrada, M. Selective serotonin reuptake inhibitors and brain hemorrhage. Neurology 79, 1862-1865 (2012).
11. van Walraven, C., Mamdani, M. M., Wells, P. S. & Williams, J. I. Inhibition of serotonin reuptake by antidepressants and retrospective cohort study. Br Med J 323, 1-6 (2001).
12. Galan, A. M. et al. Serotonergic mechanisms enhance platelet-mediated thrombogenicity. Thromb Haemost 102, 511-519 (2009).
13. Maurer-Spurej, E. Serotonin reuptake inhibitors and cardiovascular diseases: A platelet connection. Cell Mol Life Sci 62, 159-170 (2005).
14. Serebruany, V. L. et al. Selective serotonin reuptake inhibitors yield additional antiplatelet protection in patients with congestive heart failure treated with antecedent aspirin. Eur J Heart Fail 5, 517-521 (2003).
15. Serebruany, V. L., O'Connor, C. M., Krishnan, R. R. & Hennekens, C. H. Hypothesis: antiplatelet effects of selective serotonin reuptake inhibitors cause clinical benefits on cardiovascular disease and increase risks of bleeding. J Cardiovasc Pharmacol Ther 10, 163-164 (2005).
16. Blanchette, C. M., Simoni-Wastila, L., Zuckerman, I. H. & Stuart, B. A secondary analysis of a duration response association between selective serotonin reuptake inhibitor use and the risk of acute myocardial infarction in the aging population. Ann Epidemiol 18, 316-321 (2008).
17. Tata, L. J. et al. General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction. Heart 91, 465-471 (2005).
18. de Abajo, F. J. Effects of selective serotonin reuptake inhibitors on platelet function: Mechanisms, clinical outcomes and implications for use in elderly patients. Drugs and Aging 28, 345-367 (2011).
19. Bismuth-Evenzal, Y. et al. Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs. J Affect Disord 136, 99-103 (2012).
20. Flöck, A. et al. Antiplatelet effects of antidepressant treatment: A randomized comparison between escitalopram and nortriptyline. Thromb Res 126, e83-e87 (2010).
21. Hallback, I., Hagg, S., Eriksson, A. C. & Whiss, P. A. INN vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation. Pharmacol Reports 64, 979-983 (2012).
22. Tseng, Y. L. et al. A selective serotonin reuptake inhibitor, citalopram, inhibits collagen-induced platelet aggregation and activation. Thromb Res 126, 517-523 (2010).
23. Tseng, Y. L., Chiang, M. L., Lane, H. Y., Su, K. P. & Lai, Y. C. Selective serotonin reuptake inhibitors reduce P2Y12 receptor-mediated amplification of platelet aggregation. Thromb Res 131, 325-332 (2013).
24. Carneiro, A. M. D., Cook, E. H., Murphy, D. L. & Blakely, R. D. Interactions between integrin αIIbβ3 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans. J Clin Invest 118, 1544-1552 (2008).
25. Dilks, J. R. & Flaumenhaft, R. Fluoxetine (Prozac) augments platelet activation mediated through protease-activated receptors. J Thromb Haemost 6, 705-708 (2008).
26. Bampalis, V. G., Khandoga, A. L. & Siess, W. Fluoxetine inhibition of 5-HT-potentiated platelet aggregation in whole blood. Thromb Haemost 104, 1272-1274 (2010).
27. Hergovich, N. et al. Paroxetine decreases platelet serotonin storage and platelet function in human beings. Clin Pharmacol Ther 68, 435-442 (2000).
28. Owens, M. J., Knight, D. L. & Nemeroff, C. B. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry 50, 345-350 (2001).
29. Knight, C. G. et al. The collagen-binding A-domains of integrins α1β1 and α2β1 recognize the same specific amino acid sequence, GFOGER, in native (triple-helical) collagens. J Biol Chem 275, 35-40 (2000).
30. Jarvis, G. E. et al. Identification of a major GpVI-binding locus in human type III collagen. Blood 111, 4986-4996 (2008).
31. Lesch, K. P., Wolozin, B. L., Murphy, D. L. & Reiderer, P. Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem 60, 2319-2322 (1993).
32. Zhong, H., Haddjeri, N. & Sánchez, C. Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter-a review of current understanding of its mechanism of action. Psychopharmacology (Berl) 219, 1-13 (2012).
33. Sánchez, C. The pharmacology of citalopram enantiomers: the antagonism by R-citalopram on the effect of S-citalopram. Basic Clin Pharmacol Toxicol 99, 91-95 (2006).
34. Montgomery, S. A., Loft, H., Sánchez, C., Reines, E. H. & Papp, M. Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model. Pharmacol Toxicol 88, 282-286 (2001).
35. Moore, N., Verdoux, H. & Fantino, B. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Int Clin Psychopharmacol 20, 131-137 (2005).
36. Jarvis, G. E. & Thompson, A. J. A golden approach to ion channel inhibition. Trends Pharmacol Sci 34, 481-488 (2013).
37. Mould, D. R. & Upton, R. N. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT pharmacometrics Syst Pharmacol 2, e38 (2013).
38. Kass, R. E. & Raftery, A. E. Bayes Factors. J Am Stat Assoc 90, 773-795 (1995).
39. Plenge, P., Gether, U. & Rasmussen, S. G. Allosteric effects of R-and S-citalopram on the human 5-HT transporter: Evidence for distinct high-and low-affinity binding sites. Eur J Pharmacol 567, 1-9 (2007).
40. Jacobsen, J. P. R. et al. The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse. Psychopharmacology (Berl) 231, 4527-4540 (2014).
41. Milne, R. J. & Goa, K. L. Citalopram. Drugs 41, 450-477 (1991).
42. Parker, N. G. & Brown, C. S. Citalopram in the treatment of depression. Ann Pharmacother 34, 761-771 (2000).
43. Oliver, K. H., Duvernay, M. T., Hamm, H. E. & Carneiro, A. M. D. Loss of serotonin transporter function alters ADP-mediated glycoprotein αIIbβ3 activation through dysregulation of the receptor. J Biol Chem 291, 20210-20219 (2016).
44. Wolf, K. et al. Partially defective store operated calcium entry and hem(ITAM) signaling in platelets of serotonin transporter deficient mice. PLoS One 11, e0147664 (2016).
45. Bonnin, A., Zhang, L., Blakely, R. D. & Levitt, P. The SSRI citalopram affects fetal thalamic axon responsiveness to netrin-1 in vitro independently of SERT antagonism. Neuropsychopharmacology 37, 1879-1884 (2012).
46. Narita, N., Hashimoto, K., Tomitaka, S. & Minabe, Y. Interactions of selective serotonin reuptake inhibitors with subtypes of sigma receptors in rat brain. Eur J Pharmacol 307, 117-119 (1996).
47. Lewandrowski, U. et al. Platelet membrane proteomics: A novel repository for functional research. Blood 114, e10-e20 (2009).
48. Roweth, H. G. et al. Putative, novel mechanisms of action for citalopram-induced platelet inhibition. Res Pract Thromb Haemost S1, 242 (2017).
49. Fagura, M. S., Jarvis, G. E., Dougall, I. G. & Leff, P. Adventures in the pharmacological analysis of P2 receptors. J Auton Nerv Syst 81, 178-186 (2000).
50. Hall, D. A. & Hourani, S. M. O. Effects of analogues of adenine nucleotides on increases in intracellular calcium mediated by P2Tpurinoceptors on human blood platelets. Br J Pharamcology 108, 728-733 (1993).
51. Cannon, C. P. et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet 375, 283-293 (2010).
52. Gasparotto, J. et al. Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation. Sci Rep 7, 8795 (2017).
53. Amin, N. A. et al. Cell-intrinsic determinants of ibrutinib-induced apoptosis in Chronic Lymphocytic Leukemia. Clin Cancer Res 23, 1049-1059 (2017).
54. Roncagalli, R. et al. Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. Nat Immunol 15, 384-392 (2014).
55. Grossmann, A. et al. Phospho-tyrosine dependent protein-protein interaction network. Mol Syst Biol 11, 1-15 (2015).
56. Huang, S. C., Tsai, H. F., Tzeng, H. T., Liao, H. J. & Hsu, P. N. Lipid Raft Assembly and Lck Recruitment in TRAIL Costimulation Mediates NF-KB Activation and T Cell Proliferation. J Immunol 186, 931-939 (2011).
57. Zheng, Y. et al. Restoration of responsiveness of phospholipase Cγ2-deficient platelets by enforced expression of phospholipase Cγ1. PLoS One 10, e0119739 (2015).
58. Yanagisawa, S. et al. Decreased phosphatase PTEN amplifies PI3K signaling and enhances pro-inflammatory cytokine release in COPD. Am J Physiol-Lung Cell Mol Physiol 313, 230-239 (2017).
59. Born, G. V. R. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194, 927-929 (1962).
60. Jarvis, G. E., Humphries, R. G., Robertson, M. J. & Leff, P. ADP can induce aggregation of human platelets via both P2Y1 and P2T receptors. Br J Pharmacol 129, 275-282 (2000).
61. Jarvis, G. E. et al. A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α2β1. J Thromb Haemost 10, 268-277 (2012).
62. Bellavite, P. et al. A colorimetric method for the measurement of platelet adhesion in microtiter plates. Anal Chem 216, 444-450 (1994).
63. DeLean, A., Munson, P. J. & Rodbard, D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol 235, 97-102 (1978).
64. Sheiner, L. B. & Beal, S. L. Pharmacokinetic parameter estimates from several least square procedures: superiority of extended least square. J Pharmacokinet Biopharm 13, 185-201 (1985).
65. Jarvis, G. E., Barbosa, R. & Thompson, A. J. Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modeling. J Pharmacol Exp Ther 356, 549-562 (2016).