Effect of Administration of Neurokinin B Agonist (Senktide) and Antagonist (Sb222200) on Hematological and Coagulation Parameters in Adult Male Rats
DOI:
https://doi.org/10.52206/jsmc.2025.15.1.986Abstract
Background: Neurokinin B is known as a regulator of reproduction, however its chronic effects on hematological and coagulation parameters in adult male mammals are not well understood
Objective: To explore the effects of Senktide (Neurokinin B agonist) and SB222200 (Neurokinin B antagonist) administration on hematological and coagulation parameters in adult rats.
Materials and Methods: This laboratory-based experimental study was conducted at Gomal University and KMU Institute of Medical Sciences from February 2019 to April 2021. Healthy adult male Sprague Dawley rats were randomly assigned to three groups (n=5 animals/group). They were administered intraperitoneally with Senktide (1µg) and SB222200 (1µg) consecutively twice daily for 12 days. Control rats received distilled water injections. The animals were sacrificed after 12-day treatment. Blood samples were collected directly from the left ventricle to analyze hematological and coagulation parameters.
Results: Senktide-treated rats showed significantly prolonged bleeding time (111±17.10sec) compared to SB222200 (27±12.55sec) and control (33±12.55sec). Clotting time was also higher (Senktide: 96±17.10sec; SB222200: 39±8.22sec; control: 42±12.55sec), as were prothrombin time [PT] (Senktide: 90±14.58sec; SB222200: 15.80±3.90sec; control: 15±4.12sec), activated partial thromboplastin time [APPT] (Senktide: 92±25.25sec; SB222200: 16.20±3.19sec; control: 19.40±2.97sec) and international normalized ratio (Senktide: 6.60±1.07; SB222200: 1.16±0.29; control: 1.10±0.30) in Senktide-treated rats. Mean platelet volume (Senktide: 8.88±0.33fl; SB222200: 7.92±0.29fl; control: 8.04±0.48fl) and leukocyte count (×10³/µl) (Senktide: 12±0.79; SB222200: 8.89±0.97; control: 8.87±1.32) were significantly elevated however platelet count (×10³/µl) (Senktide: 792.20±50.39; SB222200: 968.60±45.33; control: 960.60±58.71) was reduced in Senktide-treated rats.
Conclusion: Senktide administration led to leukocytosis, thromboctopenia, and affected coagulation pathways with prolonged BT, CT, PT and APTT.
Keywords: Activated Partial Thromboplastin Time, Blood Coagulation, Blood Coagulation Tests, Neurokinin B, Platelets, Prothrombin Time, Senktide, SB222200, Tachykinins.
References
Almeida TA, Rojo J, Nieto PM, Pinto FM, Hernandez M, Martín JD, et al. Tachykinins and tachykinin receptors: structure and activity relationships. Curr Med Chem 2004;11(15):2045-81. https://doi.org/10.2174/0929867043364748
Page NM, Woods RJ, Gardiner SM, Lomthaisong K, Gladwell RT, Butlin DJ, et al. Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia. Nature 2000;405(6788): 797-800. https://doi.org/10.1038/35015579
Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet 2009;41(3):354-8. https://doi.org/10.1038/ng.306
Young J, Bouligand J, Francou B, Raffin-Sanson ML, Gaillez S, Jeanpierre M, et al. TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. J Clin Endocrinol Metab 2010;95(5):2287-95. https://doi.org/10.1210/jc.2009-2600
Ruiz-Pino F, Garcia-Galiano D, Manfredi-Lozano M, Leon S, Sánchez-Garrido MA, Roa J, et al. Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats. Endocrinology 2015;156(2):576-88. https://doi.org/10.1210/en.2014-1026
Skorupskaite K, George J, Anderson RA. Role of a neurokinin B receptor antagonist in the regulation of ovarian function in healthy women. Lancet 2015; 385 Suppl 1:S92. https://doi.org/10.1016/s0140-6736(15)60407-x
Santen RJ, Stuenkel CA, Davis SR, Pinkerton JV, Gompel A, Lumsden MA. Managing Menopausal Symptoms and Associated Clinical Issues in Breast Cancer Survivors. J Clin Endocrinol Metab 2017; 102(10):3647-61. https://doi.org/10.1210/jc.2017-01138
Brain SD. Sensory neuropeptides: their role in inflammation and wound healing. Immunopharmacology 1997;37(2):133-52. https://doi.org/10.1016/S0162-3109(97)00055-6
Graham GJ, Stevens JM, Page NM, Grant AD, Brain SD, Lowry PJ, et al. Tachykinins regulate the function of platelets. Blood 2004;104(4):1058-65. https://doi.org/10.1182/blood-2003-11-3979
Bost KL. Tachykinin-mediated modulation of the immune response. Front Biosci-Landmark (FBL) 2004;9(6):3331-2. https://doi.org/10.2741/1484
Feng F, Yang J, Tong L, Yuan S, Tian Y, Hong L, et al. Substance P immunoreactive nerve fibres are related to gastric cancer differentiation status and could promote proliferation and migration of gastric cancer cells. Cell Biol Int 2011;35(6):623-9. https://doi.org/10.1042/CBI20100229
Jones S, Tucker KL, Sage T, Kaiser WJ, Barrett NE, Lowry PJ, et al. Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation. Blood 2008;111(2):605-12. https://doi.org/10.1182/blood-2007-07-103424
Mahmood R, Mahmood A, Khan M, Ali S, Khan SA, Jaffar SR. Rare bleeding disorders: spectrum of disease and clinical manifestations in the Pakistani population. Blood Res. 2020;55(3):146-50. https://doi.org/10.5045/br.2020.2020035
European Animal Research Association. EU regulations on animal research London, England: European Animal Research Association; https://www.eara.eu/animal-research-law
Jy W, Bidot CJ, Jr., Nunez S, Johansen ME, Horstman LL, Ahn YS. Red Cell-Derived Microparticles (RMP) As Hemostatic Agent: Evaluation in a Rabbit Ear Bleeding Model. Blood 2012;120(21):2238-. https://doi.org/10.1182/blood.V120.21.2238.2238
Ramzan F, Atta T, Luqman MW, Ramzan MH. Effects of Variable Doses of Neurokinin B on Hematological and Coagulation Parameters in Adult Male Rats. Pakistan Armed Forces Medical Journal 2024;74(5):1414-9. https://doi.org/10.51253/pafmj.v74i5.12328
Laffan MA, Manning RA. 18 - Investigation of Haemostasis. In: Bain BJ, Bates I, Laffan MA, editors. Dacie and Lewis Practical Haematology (Twelfth Edition): Elsevier; 2017. p. 366-409. https://doi.org/10.1016/B978-0-7020-6696-2.00018-7
Watson H, Culligan D, Manson L. Haematology and transfusion medicine. In: Penman ID, Ralston SH, Strachan MWJ, Hobson R, editors. Davidson's Principles and Practice of Medicine. 24th ed. London, UK: Elsevier. 2023. p. 921-88.
Lv B, Guo FF, Lin JC, Jing F. Efficacy and safety of argatroban in treatment of acute ischemic stroke: A meta-analysis. World J Clin Cases 2022;10(2): 585-93. https://doi.org/10.12998/wjcc.v10.i2.585
Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% Sodium Citrate Concentration on Routine Coagulation Testing. Am J Clin Pathol 1997; 107(1):105-10. https://doi.org/10.1093/ajcp/107.1.105
Levin J, Bessman JD. The inverse relation between platelet volume and platelet number. Abnormalities in hematologic disease and evidence that platelet size does not correlate with platelet age. J Lab Clin Med 1983;101(2):295-307.
Castelli R, Cassinerio E, Cappellini MD, Porro F, Graziadei G, Fabris F. Heparin induced thrombocytopenia: pathogenetic, clinical, diagnostic and therapeutic aspects. Cardiovasc Hematol Dis Drug Targets 2007;7(3):153-62. https://doi.org/10.2174/187152907781745251
Verheul HM, Pinedo HM. The importance of platelet counts and their contents in cancer. Clin Cancer Res 2003;9(9):3219-21.
Letai A, Kuter DJ. Cancer, Coagulation, and Anticoagulation. Oncologist. 1999;4(6):443-9. https://doi.org/10.1634/theoncologist.4-6-443
Jones S, Gibbins JM. The neurokinin 1 receptor: a potential new target for anti-platelet therapy? Curr Opin Pharmacol 2008;8(2):114-9. https://doi.org/10.1016/j.coph.2008.01.004
Brunelleschi S, Tarli S, Giotti A, Fantozzi R. Priming effects of mammalian tachykinins on human neutrophils. Life Sci 1991;48(2):PL1-PL5. https://doi.org/10.1016/0024-3205(91)90416-9
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 The authors retain the copyrights. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on their website), as it can lead to productive exchanges, as well as greater citation of published work.

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Readers may “Share-copy and redistribute the material in any medium or format” and “Adapt-remix, transform, and build upon the material”. The readers must give appropriate credit to the source of the material and indicate if changes were made to the material. Readers may not use the material for commercial purpose. The readers may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.