DOI QR코드

DOI QR Code

Feline Interstitial Cystitis Enhances Mucosa-Dependent Contractile Responses to Serotonin

  • Ikeda, Youko (Division of Renal-Electrolyte, Department of Medicine, School of Medicine, University of Pittsburgh) ;
  • Wolf-Johnston, Amanda (Division of Renal-Electrolyte, Department of Medicine, School of Medicine, University of Pittsburgh) ;
  • Roppolo, James R. (Department of Pharmacology and Chemical Biology, University of Pittsburgh) ;
  • Buffington, Charles A.T. (Department of Veterinary Clinical Sciences, The Ohio State University) ;
  • Birder, Lori (Division of Renal-Electrolyte, Department of Medicine, School of Medicine, University of Pittsburgh)
  • Received : 2018.12.08
  • Accepted : 2018.12.13
  • Published : 2018.12.31

Abstract

Purpose: To determine whether responses to serotonin are altered in bladder strips from cats diagnosed with a naturally occurring form of bladder pain syndrome/interstitial cystitis termed feline interstitial cystitis (FIC). Methods: Full thickness bladder strips were isolated from aged matched healthy control cats and cats with clinically verified FIC. Bladder strips were mounted in an organ bath and connected to a tension transducer to record contractile activity. A serotonin dose response ($0.01-10{\mu}M$) was determined for each strip with the mucosa intact or denuded. Results: Bladder strips from control and FIC cats contracted in response to serotonin in a dose-dependent manner. The normalized force of serotonin-evoked contractions was significantly greater in bladder strips from cats with FIC (n=7) than from control cats (n=4). Removal of the mucosa significantly decreased serotonin-mediated responses in both control and FIC bladder preparations. Furthermore, the contractions in response to serotonin were abolished by $1{\mu}M$ atropine in both control and FIC bladder strips. Conclusions: The effect of serotonin on contractile force, but not sensitivity, was potentiated in bladder strips from cats with FIC, and was dependent upon the presence of the mucosa in control and FIC groups. As atropine inhibited these effects of serotonin, we hypothesize that, serotonin enhances acetylcholine release from the mucosa of FIC cat bladder strips, which could account for the increased force generated. In summary, FIC augments the responsiveness of bladder to serotonin, which may contribute to the symptoms associated with this chronic condition.

Keywords

Acknowledgement

Supported by : NIDDK

References

  1. de Groat WC. Influence of central serotonergic mechanisms on lower urinary tract function. Urology 2002;59(5 Suppl 1):30-6. https://doi.org/10.1016/S0090-4295(01)01636-3
  2. Michel MC, Peters SL. Role of serotonin and noradrenaline in stress urinary incontinence. BJU Int 2004;94 Suppl 1:23-30. https://doi.org/10.1111/j.1464-410X.2004.04811.x
  3. Kim HJ, Lee G, Kim DH, Lee SJ, Yoon DK, Cho JH. Acute effects of serotonin on rat bladder contractility. Urol Int 2002;68:44-8. https://doi.org/10.1159/000048416
  4. Lychkova AE, Pavone LM. Role of serotonin receptors in regulation of contractile activity of urinary bladder in rabbits. Urology 2013;81:696.e13-8. https://doi.org/10.1016/j.urology.2012.11.029
  5. Yoshida A, S-Yamashita Y, Kaibara M, Taniyama K, Tanaka N. 5-Hydroxytryptamine receptors, especially the 5-HT4 receptor, in guinea pig urinary bladder. Jpn J Pharmacol 2002;89:349-55. https://doi.org/10.1254/jjp.89.349
  6. Michishita M, Yano K, Kasahara K, Tomita K, Matsuzaki O. Increased expression of 5-HT(2A) and 5-HT(2B) receptors in detrusor muscle after partial bladder outlet obstruction in rats. Biomed Res 2015;36:187-94. https://doi.org/10.2220/biomedres.36.187
  7. Moro C, Edwards L, Chess-Williams R. 5-HT2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria. Int J Urol 2016;23:946-51. https://doi.org/10.1111/iju.13172
  8. Khan MA, Dashwood MR, Thompson CS, Mumtaz FH, Morgan RJ, Mikhailidis DP. Time-dependent up-regulation of neuronal 5-hydroxytryptamine binding sites in the detrusor of a rabbit model of partial bladder outlet obstruction. World J Urol 1999;17:255-60. https://doi.org/10.1007/s003450050142
  9. Imamura T, Ishizuka O, Ogawa T, Minagawa T, Ishikawa M, Hiragata S, et al. Expression of 5-hydroxytryptamine receptors in human urinary bladders with benign prostatic hyperplasia. Adv Ther 2015;32 Suppl 1:29-37. https://doi.org/10.1007/s12325-015-0242-0
  10. Lonne-Rahm SB, Rickberg H, El-Nour H, Marin P, Azmitia EC, Nordlind K. Neuroimmune mechanisms in patients with atopic dermatitis during chronic stress. J Eur Acad Dermatol Venereol 2008;22:11-8.
  11. Theoharides TC, Cochrane DE. Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol 2004;146:1-12. https://doi.org/10.1016/j.jneuroim.2003.10.041
  12. Erickson DR, Tomaszewski JE, Kunselman AR, Stetter CM, Peters KM, Rovner ES, et al. Urine markers do not predict biopsy findings or presence of bladder ulcers in interstitial cystitis/painful bladder syndrome. J Urol 2008;179:1850-6. https://doi.org/10.1016/j.juro.2008.01.047
  13. Buffington CA. Comorbidity of interstitial cystitis with other unexplained clinical conditions. J Urol 2004;172(4 Pt 1):1242-8. https://doi.org/10.1097/01.ju.0000137953.49304.6c
  14. Westropp JL, Welk KA, Buffington CA. Small adrenal glands in cats with feline interstitial cystitis. J Urol 2003;170(6 Pt 1):2494-7. https://doi.org/10.1097/01.ju.0000095566.63870.66
  15. Cohen ML, Drey K. Contractile responses in bladder body, bladder neck and prostate from rat, guinea pig and cat. J Pharmacol Exp Ther 1989;248:1063-8.
  16. D'Agostino G, Condino AM, Gallinari P, Franceschetti GP, Tonini M. Characterization of prejunctional serotonin receptors modulating [3H]acetylcholine release in the human detrusor. J Pharmacol Exp Ther 2006;316:129-35. https://doi.org/10.1124/jpet.105.092551
  17. Matsumoto-Miyai K, Yamada E, Shinzawa E, Koyama Y, Shimada S, Yoshizumi M, et al. Serotonergic regulation of distention-induced ATP release from the urothelium. Am J Physiol Renal Physiol 2016;310:F646-55. https://doi.org/10.1152/ajprenal.00024.2015
  18. Buffington CA, Chew DJ, Kendall MS, Scrivani PV, Thompson SB, Blaisdell JL, et al. Clinical evaluation of cats with nonobstructive urinary tract diseases. J Am Vet Med Assoc 1997;210:46-50.
  19. Birder LA, Barrick SR, Roppolo JR, Kanai AJ, de Groat WC, Kiss S, et al. Feline interstitial cystitis results in mechanical hypersensitivity and altered ATP release from bladder urothelium. Am J Physiol Renal Physiol 2003;285:F423-9. https://doi.org/10.1152/ajprenal.00056.2003
  20. Ikeda Y, Birder L, Buffington C, Roppolo J, Kanai A. Mucosal muscarinic receptors enhance bladder activity in cats with feline interstitial cystitis. J Urol 2009;181:1415-22. https://doi.org/10.1016/j.juro.2008.10.138
  21. Sun Y, Chai TC. Augmented extracellular ATP signaling in bladder urothelial cells from patients with interstitial cystitis. Am J Physiol Cell Physiol 2006;290:C27-34. https://doi.org/10.1152/ajpcell.00552.2004
  22. Mansfield KJ, Hughes JR. Effect of inflammatory mediators on ATP release of human urothelial RT4 cells. Biomed Res Int 2014;2014:182862.
  23. Coelho A, Oliveira R, Cavaleiro H, Cruz CD, Cruz F. Evidence for an urethro-vesical crosstalk mediated by serotonin. Neurourol Urodyn 2018;37:2389-97. https://doi.org/10.1002/nau.23590
  24. Kullmann FA, Chang HH, Gauthier C, McDonnell BM, Yeh JC, Clayton DR, et al. Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing. Acta Physiol (Oxf) 2018 Feb;222(2). https://doi.org/10.1111/apha.12919.
  25. van Ophoven A, Hertle L. The dual serotonin and noradrenaline reuptake inhibitor duloxetine for the treatment of interstitial cystitis: results of an observational study. J Urol 2007;177:552-5.
  26. Papandreou C, Skapinakis P, Giannakis D, Sofikitis N, Mavreas V. Antidepressant drugs for chronic urological pelvic pain: an evidencebased review. Adv Urol 2009;2009:797031.
  27. Hanna-Mitchell AT, Beckel JM, Barbadora S, Kanai AJ, de Groat WC, Birder LA. Non-neuronal acetylcholine and urinary bladder urothelium. Life Sci 2007;80:2298-302. https://doi.org/10.1016/j.lfs.2007.02.010
  28. Lips KS, Wunsch J, Zarghooni S, Bschleipfer T, Schukowski K, Weidner W, et al. Acetylcholine and molecular components of its synthesis and release machinery in the urothelium. Eur Urol 2007;51:1042-53. https://doi.org/10.1016/j.eururo.2006.10.028
  29. McLatchie LM, Young JS, Fry CH. Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations. Br J Pharmacol 2014;171:3394-403. https://doi.org/10.1111/bph.12682
  30. Young JS, Matharu R, Carew MA, Fry CH. Inhibition of stretchingevoked ATP release from bladder mucosa by anticholinergic agents. BJU Int 2012;110(8 Pt B):E397-401. https://doi.org/10.1111/j.1464-410X.2012.10966.x

Cited by

  1. A Message From the New Editor-in-Chief vol.23, pp.3, 2018, https://doi.org/10.5213/inj.1920edi.006