Glycine transporter type 2 (GlyT2) inhibitor ameliorates bladder overactivity and nociceptive behavior in rats.

European Urology
Satoru YoshikawaNaoki Yoshimura

Abstract

Glycine is a major inhibitory neurotransmitter in the spinal cord, the concentration of which is regulated by two types of glycine transporters (GlyTs): GlyT1 and GlyT2. We hypothesized that the inhibition of GlyTs could ameliorate bladder overactivity and/or pain sensation in the lower urinary tract. Investigate the effects of GlyT inhibitors on bladder overactivity and pain behavior in rats. Cystometry was performed under urethane anesthesia in cyclophosphamide (CYP)-treated rats. In behavioral studies using conscious rats, nociceptive responses were induced by intravesical administration of resiniferatoxin (3μM). Selective GlyT1 or GlyT2 inhibitors were administered intrathecally to evaluate their effects. Cystometric parameters, nociceptive behaviors (licking and freezing), and messenger RNA (mRNA) levels of GlyTs and glycine receptor (GlyR) subunits in the dorsal spinal cord (L6-S1) were measured. During cystometry in CYP-treated rats, significant increases in intercontraction interval and micturition pressure threshold were elicited by ALX-1393, a selective GlyT2 inhibitor, but not by sarcosine, a GlyT1 inhibitor. These effects were completely reversed by strychnine, a GlyR antagonist. ALX-1393 also significantly suppress...Continue Reading

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Citations

Nov 1, 2013·Nature Reviews. Drug Discovery·Robert J Harvey, Benjamin K Yee
Nov 5, 2015·Expert Opinion on Emerging Drugs·Teruyuki OgawaNaoki Yoshimura
Feb 5, 2016·International Urology and Nephrology·Masashi HondaAtsushi Takenaka
May 9, 2014·International Journal of Urology : Official Journal of the Japanese Urological Association·Naoki YoshimuraTeruyuki Ogawa
Jun 27, 2015·Nature Reviews. Drug Discovery·Lawrence LinKathleen M Giacomini
Jul 9, 2013·Neurourology and Urodynamics·Naoki YoshimuraSatoru Yoshikawa
Jul 31, 2014·Anesthesia and Analgesia·Naoyo MotoyamaToshihiro Dohi
Aug 10, 2017·Cellular and Molecular Life Sciences : CMLS·Hanns Ulrich ZeilhoferGonzalo E Yévenes
Aug 23, 2018·Neurourology and Urodynamics·Karl-Erik AnderssonKevin Rademakers
Dec 22, 2016·Neuronal Signaling·Francisco ZafraCecilio Giménez
May 19, 2021·ACS Chemical Neuroscience·Cristina Benito-MuñozBeatriz López-Corcuera
Sep 7, 2017·Journal of Medicinal Chemistry·Christopher L Cioffi

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