International Neurourology Journal

Korean Continence Society (대한배뇨장애요실금학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of High Concentrations of Naftopidil on Dorsal Root-Evoked Excitatory Synaptic Transmissions in Substantia Gelatinosa Neurons In Vitro

  • Uta, Daisuke (Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama) ;
  • Hattori, Tsuyoshi (Department of Medical Affairs, Asahi Kasei Pharma Co.) ;
  • Yoshimura, Megumu (Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University)
  • Received : 2018.06.29
  • Accepted : 2018.09.18
  • Published : 2018.12.31
⟨ Previous Next ⟩

Abstract

Purpose: Naftopidil ((${\pm}$)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated. Methods: Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in $A{\delta}$ or C fibers. Naftopidil or prazosin, an ${\alpha}1$-adrenoceptor blocker, was perfused at $100{\mu}M$ or $10{\mu}M$, respectively. Results: Bath-applied $100{\mu}M$ naftopidil significantly decreased the peak amplitudes of $A{\delta}$ and C fiber-evoked EPSCs to $72.0%{\pm}7.1%$ (n=15) and $70.0%{\pm}5.5%$ (n=20), respectively, in a reversible and reproducible manner. Bath application of $100{\mu}M$ prazosin did not inhibit $A{\delta}$ or C fiber-evoked EPSCs. Conclusions: The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve ${\alpha}1$-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.

Keywords

Acknowledgement

Supported by : Ministry of Education, Science, Sports and Culture of Japan, MEXT

References

  1. Agarwal A, Eryuzlu LN, Cartwright R, Thorlund K, Tammela TL, Guyatt GH, et al. What is the most bothersome lower urinary tract symptom? Individual- and population-level perspectives for both men and women. Eur Urol 2014;65:1211-7. https://doi.org/10.1016/j.eururo.2014.01.019
  2. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002;21:167-78. https://doi.org/10.1002/nau.10052
  3. Caine M. Alpha-adrenergic blockers for the treatment of benign prostatic hyperplasia. Urol Clin North Am 1990;17:641-9.
  4. Majima T, Yamamoto T, Funahashi Y, Takai S, Matsukawa Y, Yoshida M, et al. Effect of naftopidil on bladder microcirculation in a rat model of bladder outlet obstruction. Low Urin Tract Symptoms 2017;9:111-6. https://doi.org/10.1111/luts.12119
  5. Okutsu H, Matsumoto S, Hanai T, Noguchi Y, Fujiyasu N, Ohtake A, et al. Effects of tamsulosin on bladder blood flow and bladder function in rats with bladder outlet obstruction. Urology 2010;75:235-40. https://doi.org/10.1016/j.urology.2009.05.045
  6. Yamanishi T, Mizuno T, Tatsumiya K, Watanabe M, Kamai T, Yoshida K. Urodynamic effects of silodosin, a new alpha 1A-adrenoceptor selective antagonist, for the treatment of benign prostatic hyperplasia. Neurourol Urodyn 2010;29:558-62.
  7. Yamanishi T, Yasuda K, Kamai T, Tsujii T, Sakakibara R, Uchiyama T, et al. Single-blind, randomized controlled study of the clinical and urodynamic effects of an alpha-blocker (naftopidil) and phytotherapy (eviprostat) in the treatment of benign prostatic hyperplasia. Int J Urol 2004;11:501-9. https://doi.org/10.1111/j.1442-2042.2004.00844.x
  8. Sun Y, MaLossi J, Jacobs SC, Chai TC. Effect of doxazosin on stretch-activated adenosine triphosphate release in bladder urothelial cells from patients with benign prostatic hyperplasia. Urology 2002;60:351-6. https://doi.org/10.1016/S0090-4295(02)01710-7
  9. Ishihama H, Momota Y, Yanase H, Wang X, de Groat WC, Kawatani M. Activation of alpha1D adrenergic receptors in the rat urothelium facilitates the micturition reflex. J Urol 2006;175:358-64.
  10. Hattori T, Sugaya K. Mechanisms of action for ${\alpha}$(1)-adrenoceptor blockers in storage symptoms with new insights into the micturition reflex. Life Sci 2017;191:90-6. https://doi.org/10.1016/j.lfs.2017.10.015
  11. Gotoh M, Kamihira O, Kinukawa T, Ono Y, Ohshima S, Origasa H, et al. Comparison of tamsulosin and naftopidil for efficacy and safety in the treatment of benign prostatic hyperplasia: a randomized controlled trial. BJU Int 2005;96:581-6. https://doi.org/10.1111/j.1464-410X.2005.05688.x
  12. ishino Y, Masue T, Miwa K, Takahashi Y, Ishihara S, Deguchi T. Comparison of two alpha1-adrenoceptor antagonists, naftopidil and tamsulosin hydrochloride, in the treatment of lower urinary tract symptoms with benign prostatic hyperplasia: a randomized crossover study. BJU Int 2006;97:747-51. https://doi.org/10.1111/j.1464-410X.2006.06030.x
  13. Takei R, Ikegaki I, Shibata K, Tsujimoto G, Asano T. Naftopidil, a novel alpha1-adrenoceptor antagonist, displays selective inhibition of canine prostatic pressure and high affinity binding to cloned human alpha1-adrenoceptors. Jpn J Pharmacol 1999;79:447-54. https://doi.org/10.1254/jjp.79.447
  14. Sugaya K, Nishijima S, Miyazato M, Ashitomi K, Hatano T, Ogawa Y. Effects of intrathecal injection of tamsulosin and naftopidil, alpha-1A and -1D adrenergic receptor antagonists, on bladder activity in rats. Neurosci Lett 2002;328:74-6. https://doi.org/10.1016/S0304-3940(02)00459-7
  15. Takao T, Tsujimura A, Kiuchi H, Takezawa K, Okuda H, Yamamoto K, et al. Correlation between overactive bladder symptoms and quality of life in Japanese male patients: focus on nocturia. Urology 2013;82:189-93. https://doi.org/10.1016/j.urology.2013.02.024
  16. Uta D, Xie DJ, Hattori T, Kasahara KI, Yoshimura M. Effects of naftopidil on inhibitory transmission in substantia gelatinosa neurons of the rat spinal dorsal horn in vitro. J Neurol Sci 2017;380:205-11. https://doi.org/10.1016/j.jns.2017.07.030
  17. Sugaya K, Nishijima S, Kadekawa K, Ashitomi K, Ueda T, Yamamoto H. Spinal mechanism of micturition reflex inhibition by naftopidil in rats. Life Sci 2014;116:106-11. https://doi.org/10.1016/j.lfs.2014.09.008
  18. Yoshimura M, Jessell TM. Primary afferent-evoked synaptic responses and slow potential generation in rat substantia gelatinosa neurons in vitro. J Neurophysiol 1989;62:96-108. https://doi.org/10.1152/jn.1989.62.1.96
  19. Nakatsuka T, Ataka T, Kumamoto E, Tamaki T, Yoshimura M. Alteration in synaptic inputs through C-afferent fibers to substantia gelatinosa neurons of the rat spinal dorsal horn during postnatal development. Neuroscience 2000;99:549-56. https://doi.org/10.1016/S0306-4522(00)00224-4
  20. Uta D, Furue H, Pickering AE, Rashid MH, Mizuguchi-Takase H, Katafuchi T, et al. TRPA1-expressing primary afferents synapse with a morphologically identified subclass of substantia gelatinosa neurons in the adult rat spinal cord. Eur J Neurosci 2010;31:1960-73. https://doi.org/10.1111/j.1460-9568.2010.07255.x
  21. Yoshimura M, Nishi S. Blind patch-clamp recordings from substantia gelatinosa neurons in adult rat spinal cord slices: pharmacological properties of synaptic currents. Neuroscience 1993;53:519-26. https://doi.org/10.1016/0306-4522(93)90216-3
  22. Yang K, Kumamoto E, Furue H, Li YQ, Yoshimura M. Action of capsaicin on dorsal root-evoked synaptic transmission to substantia gelatinosa neurons in adult rat spinal cord slices. Brain Res 1999;830:268-73. https://doi.org/10.1016/S0006-8993(99)01408-0
  23. Galvao J, Davis B, Tilley M, Normando E, Duchen MR, Cordeiro MF. Unexpected low-dose toxicity of the universal solvent DMSO. FASEB J 2014;28:1317-30. https://doi.org/10.1096/fj.13-235440
  24. Yang K, Kumamoto E, Furue H, Yoshimura M. Capsaicin facilitates excitatory but not inhibitory synaptic transmission in substantia gelatinosa of the rat spinal cord. Neurosci Lett 1998;255:135-8. https://doi.org/10.1016/S0304-3940(98)00730-7
  25. Willis WD. John Eccles' studies of spinal cord presynaptic inhibition. Prog Neurobiol 2006;78:189-214. https://doi.org/10.1016/j.pneurobio.2006.02.007
  26. Sakai T, Kasahara K, Tomita K, Ikegaki I, Kuriyama H. Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats. Eur J Pharmacol 2013;700:194-200. https://doi.org/10.1016/j.ejphar.2012.12.022
  27. Abe K, Kato G, Katafuchi T, Tamae A, Furue H, Yoshimura M. Responses to 5-HT in morphologically identified neurons in the rat substantia gelatinosa in vitro. Neuroscience 2009;159:316-24. https://doi.org/10.1016/j.neuroscience.2008.12.021
  28. Fukushima T, Ohtsubo T, Tsuda M, Yanagawa Y, Hori Y. Facilitatory actions of serotonin type 3 receptors on GABAergic inhibitory synaptic transmission in the spinal superficial dorsal horn. J Neurophysiol 2009;102:1459-71. https://doi.org/10.1152/jn.91160.2008
  29. Ito A, Kumamoto E, Takeda M, Shibata K, Sagai H, Yoshimura M. Mechanisms for ovariectomy-induced hyperalgesia and its relief by calcitonin: participation of 5-HT1A-like receptor on C-afferent terminals in substantia gelatinosa of the rat spinal cord. J Neurosci 2000;20:6302-8. https://doi.org/10.1523/JNEUROSCI.20-16-06302.2000
  30. Xie DJ, Uta D, Feng PY, Wakita M, Shin MC, Furue H, et al. Identification of 5-HT receptor subtypes enhancing inhibitory transmission in the rat spinal dorsal horn in vitro. Mol Pain 2012;8:58.
  31. Alarayyed NA, Graham BR, Prichard BN, Smith CC. The potentiation of adrenaline-induced in vitro platelet aggregation by ADP, collagen and serotonin and its inhibition by naftopidil and doxazosin in normal human subjects. Br J Clin Pharmacol 1995;39:369-74. https://doi.org/10.1111/j.1365-2125.1995.tb04464.x
  32. Kanda H, Ishii K, Ogura Y, Imamura T, Kanai M, Arima K, et al. Naftopidil, a selective alpha-1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest. Int J Cancer 2008;122:444-51. https://doi.org/10.1002/ijc.23095
  33. Yamada D, Nishimatsu H, Kumano S, Hirano Y, Suzuki M, Fujimura T, et al. Reduction of prostate cancer incidence by naftopidil, an ${\alpha}1$-adrenoceptor antagonist and transforming growth $factor-{\beta}$ signaling inhibitor. Int J Urol 2013;20:1220-7. https://doi.org/10.1111/iju.12156
  34. van de Merwe JP, Nordling J, Bouchelouche P, Bouchelouche K, Cervigni M, Daha LK, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol 2008;53:60-7. https://doi.org/10.1016/j.eururo.2007.09.019

Cited by

  1. Characterization on Responsiveness of Excitatory Synaptic Transmissions to α1-Adrenoceptor Blockers in Substantia Gelatinosa Neurons Isolated From Lumbo-Sacral Level in Rat Spinal Cords vol.23, pp.1, 2018, https://doi.org/10.5213/inj.1938056.028
  2. Differential Effects of Alpha 1-Adrenoceptor Antagonists on the Postsynaptic Sensitivity: Using Slice Patch-Clamp Technique for Inhibitory Postsynaptic Current in Substantia Gelatinosa Neurons From Lu vol.24, pp.2, 2018, https://doi.org/10.5213/inj.1938248.124
  3. Effect of Alpha 1-Adrnoceptor Antagonists on Postsynaptic Sensitivity in Substantia Gelatinosa Neurons From Lumbosacral Spinal Cord in Rats Using Slice Patch-Clamp Technique for mEPSC vol.24, pp.2, 2020, https://doi.org/10.5213/inj.1938250.125
  4. Analyses of the Mode of Action of an Alpha-Adrenoceptor Blocker in Substantia Gelatinosa Neurons in Rats vol.22, pp.17, 2018, https://doi.org/10.3390/ijms22179636