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Regulatory Effects of 5-Hydroxytryptamine Receptors on Voiding Function

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Abstract

A growing body of evidence suggests that 5-hydroxytryptamine (5-HT; serotonin) has both physiological and pathological functions in the lower urinary tract. A wide variety of 5-HT receptor subtypes are variably expressed in different organs, both peripheral and central. On urinary bladder smooth muscle, 5-HT1A, 5-HT2, 5-HT3, and 5-HT7 subtypes could function as postjunctional receptors. Postjunctional 5-HT2 receptors induce detrusor contraction of the bladder body. 5-HT1A is suggested to have a similar effect to 5-HT2, while 5-HT3 might suppress detrusor contraction evoked by direct muscle stimulation. Postjunctional 5-HT7 is reported to induce relaxation of the bladder neck, which might be required for efficient voiding. 5-HT1A, 5-HT2A, 5-HT2C, 5-HT3, 5-HT4, and 5-HT7 subtypes also could act as prejunctional receptors in autonomic excitatory nerve terminals. 5-HT2A, 5-HT2C, 5-HT3, 5-HT4, and 5-HT7 subtypes facilitate the neurogenic contraction of the detrusor by enhancing cholinergic or purinergic transmission, whereas 5-HT1A receptors might inhibit the release of acetylcholine in the detrusor. Furthermore, 5-HT1D could be involved in the suppression of ATP release from the urothelium, aiding visceral sensation of the urinary bladder. In the central pathways controlling the micturition reflex, 5-HT1A, 5-HT2A, and 5-HT7 are involved in regulation of bladder and urethral sphincter activities. Their functions, especially that of 5-HT1A, vary in a species- and site (spinal or supraspinal)- dependent manner. In addition to urinary bladder, 5-HT could be involved in prostate contraction and cell proliferation. Evidence indicates that 5-HT receptor subtypes may be novel therapeutic targets for lower urinary tract symptoms.

Funding

Grants-in-Aid for Scientific Research (C) (KAKENHI 23590707, 24590722, and 26460694) from the Japan Society for the Promotion of Science.

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Acknowledgments

Sponsorship for this study was funded by Grants-in-Aid for Scientific Research (C) (KAKENHI 23590707, 24590722, and 26460694) from the Japan Society for the Promotion of Science. Article processing charges were funded by Asahi Kasei Pharma Corporation. Tim Werry and Springer Healthcare provided assistance with English language editing.

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

This supplement was supported by Asahi Kasei Pharma Corp. Prior to peer review, Asahi Kasei Pharma Corp were offered the opportunity to review this paper for scientific accuracy. No changes were made as a result.

Disclosures

K. Matsumoto-Miyai, M. Yoshizumi and M. Kawatani have no disclosures or financial relationships to declare.

Compliance with ethics guidelines

This article is based on previously conducted studies. All institutional and national guidelines for the care and use of laboratory animals were followed in our unpublished study cited in this article.

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Correspondence to Kazumasa Matsumoto-Miyai.

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Matsumoto-Miyai, K., Yoshizumi, M. & Kawatani, M. Regulatory Effects of 5-Hydroxytryptamine Receptors on Voiding Function. Adv Ther 32 (Suppl 1), 3–15 (2015). https://doi.org/10.1007/s12325-015-0240-2

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