Characterization of muscarinic and P2X receptors in the urothelium and detrusor muscle of the rat bladder

Ogoda, Masaki; Ito, Yoshihiko; Fuchihata, Yusuke; Onoue, Satomi; Yamada, Shizuo

doi:10.1016/j.jphs.2016.04.020

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…In the CYP-treated rats, bladder demonstrated severe epithelial ulceration, haemorrhage, inflammatory cells infiltration, submucosal oedema and desquamated granular uroepithelium cells 43 . CYP treatment may significantly increase neuronal activity in the bladder 44 . Inflammation and haemorrhage could not be prevented completely in the bladder tissues of groups 6, 7 and 8 that were given CYP + HT, while damage and changes in the bladder tissue decreased further as HT dose increased (Figures 1-3).…”

Section: Discussionmentioning

confidence: 99%

Investigation of uroprotective effects of seed methanol extracts of Hypericum triquetrifolium Turra. on cyclophosphamide-induced bladder hemorrhagic cystitis and nephrotoxicity in Wistar albino rats

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et al. 2020

Cukurova Medical Journal

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ÖzPurpose: This study investigated the possible uroprotective effects of Hypericum triquetrifolium Turra. (HT) seed methanol extracts (25,50,100 mg/kg, i.p., for 6 days) against cyclophosphamide (CYP)-induced (150 mg/kg, single dose, i.p.) acute bladder hemorrhagic cystitis (HC) and nephrotoxicity in rats. Materials and Methods: Wistar albino rats used in this study were divided into nine groups, each including seven rats. Group 1 (control) was treated with 0.5ml saline (SF) and Group 2 was treated with CYP (150 mg/kg). Groups 3, 4, 5 were treated with 25, 50, 100 mg/kg HT, respectively while groups 6, 7, 8 were treated with 25, 50, 100 mg/kg CYP + HT, respectively. Finally, Group 9 (control-2) was treated with 0.5ml-%0.2 dimethyl sulfoxide (DMSO). The serum creatinine, blood urea nitrogen (BUN), superoxide dismutase (SOD) and catalase (CAT) levels were measured in blood serum. Results: The CYP-treated rats histopathologically had mild-moderate bladder and renal injuries. The serum creatinine and BUN levels, which are the biochemical markers of renal injury, significantly increased compared to the control group. Conclusion:HT showed a protective effect on CYPrelated bladder HC and nephrotoxicity in rats by inhibiting inflammation and apoptosis. Amaç: Bu çalışmada, Hypericum triquetrifolium Turra (HT) tohum metanol ekstraktlarının (25,50,100 mg/kg, i.p., 6 gün boyunca) siklofosfamid (CYP) nedenli (150 mg/kg, tek doz, i.p.) akut mesane hemorajik sistit (HC) ve nefrotoksisiteye karşı olası üroprotektif etkileri araştırıldı. Gereç ve Yöntem: Bu çalışmada kullanılan Wistar albino sıçanlar, her biri yedi sıçan olmak üzere dokuz gruba ayrıldı. Grup 1 (kontrol) 0.5ml salin (SF) ile muamele edildi ve Grup 2, CYP (150 mg/kg) ile muamele edildi. Grup 3, 4, 5 sırasıyla 25, 50, 100 mg/kg HT ile tedavi edilirken, grup 6, 7, 8 sırasıyla 25, 50, 100 mg/kg HT + CYP ile tedavi edildi. Son olarak, Grup 9 (kontrol-2) 0.5ml-% 0.2 dimetil sülfoksit (DMSO) ile muamele edildi. Kan serumunda serum kreatinin, kan üre azotu (BUN), süperoksit dismutaz (SOD) ve katalaz (CAT) seviyeleri ölçüldü. Bulgular: CYP ile tedavi edilen sıçanların histopatolojik olarak hafif-orta derecede mesane ve böbrek yaralanmaları vardı. Böbrek hasarının biyokimyasal belirteçleri olan serum kreatinin ve BUN düzeyleri, kontrol grubuna göre önemli ölçüde artmıştır. Sonuç: HT, enflamasyonu ve apoptozu inhibe ederek sıçanlarda CYP ile ilişkili mesane HC'si ve nefrotoksisite üzerinde koruyucu bir etki göstermiştir.

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Section: Discussionmentioning

confidence: 99%

Investigation of uroprotective effects of seed methanol extracts of Hypericum triquetrifolium Turra. on cyclophosphamide-induced bladder hemorrhagic cystitis and nephrotoxicity in Wistar albino rats

Yıldız

Keskin

Şahıntürk

et al. 2020

Cukurova Medical Journal

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Optogenetic urothelial cell stimulation induces bladder contractions and pelvic nerve afferent firing

Robilotto

Yang

Alom

et al. 2023

American Journal of Physiology-Renal Physiology

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Urothelial cells, which play an essential role in the barrier function, are also thought to play a sensory role in bladder physiology by releasing signaling molecules in response to sensory stimuli that act upon adjacent sensory neurons. However, it is challenging to study this communication due to the overlap in receptor expression and proximity of urothelial cells to sensory neurons. To overcome this challenge, we have developed a mouse model where we can directly stimulate urothelial cells using optogenetics. We have crossed a uroplakin II-cre mouse (UPK2-Cre) with a mouse that expresses the light-activated cation channel, Channelrhodopsin-2 (ChR2), in the presence of cre-expression. Optogenetic stimulation of urothelial cells cultured from UPK2-ChR2 initiates cellular depolarization and release of adenosine triphosphate. Cystometry recordings demonstrate that optical stimulation of urothelial cells increases bladder pressure and pelvic nerve activity. Increases in bladder pressure persisted, albeit to a lesser extent, when the bladder was excised in an in vitro preparation. The P2X receptor antagonist, PPADS, significantly reduced optically evoked bladder contractions in vivo and ex vivo. Further, corresponding nerve activity was also inhibited with PPADS. Our data suggest that urothelial cells can initiate robust bladder contractions via sensory nerve signaling or contractions through local signaling mechanisms. This data supports a foundation of literature demonstrating communication between sensory neurons and urothelial cells. Importantly, with further use of these optogenetic tools, we hope to scrutinize this signaling mechanism, its importance for normal micturition and nociception, and how it may be altered in pathophysiologic conditions.

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The mast cell stimulator compound 48/80 causes urothelium-dependent increases in murine urinary bladder contractility

Jones

Mingin

Tykocki

2023

American Journal of Physiology-Renal Physiology

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Mast cells and degranulation of pre-formed inflammatory mediators contribute to lower urinary tract symptoms. This study investigates pathways by which the mast cell stimulator Compound 48/80 alters urinary bladder smooth muscle contractility via mast cell activation. We hypothesized that: (1) mast cell degranulation will cause spontaneous urinary bladder smooth muscle contractions; and (2) these contractions are caused by urothelium-derived PGE2. Urothelium intact and denuded urinary bladder strips were collected from mast cell sufficient (C57Bl/6) and deficient (B6.Cg-Kitw-sh) mice to determine if Compound 48/80 altered urinary bladder smooth muscle (UBSM) contractility. Electrical field stimulation was used to assess the effects of Compound 48/80 on nerve-evoked contractions. Antagonists/inhibitors were utilized to identify prostanoid signaling pathways activated or if direct activation of nerves was involved. Compound 48/80 caused slow-developing contractions, increased phasic activity, and augmented nerve-evoked responses in both mast cell sufficient and deficient mice. Nerve blockade had no effect on these responses; however, they were eliminated by removing the urothelium. Blocking P2 purinoreceptors, cyclooxygenases, or G protein signaling abolished Compound 48/80 responses. However, only combined blockade of prostaglandin E2 (EP1), prostaglandin F2α (FP), and thromboxane A2 (TP) receptors inhibited Compound 48/80 induced responses. Thus, the effects of compound 48/80 are urothelium dependent, but independent of mast cells. Further, these effects are mediated by druggable inflammatory pathways that may be used to manage inflammatory non-neurogenic bladder hyperactivity. Finally, these data strongly suggest that great care must be taken when using Compound 48/80 to determine mast cell-dependent responses in the urinary bladder.

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Characterization of muscarinic and P2X receptors in the urothelium and detrusor muscle of the rat bladder

Cited by 3 publications

References 23 publications

Investigation of uroprotective effects of seed methanol extracts of Hypericum triquetrifolium Turra. on cyclophosphamide-induced bladder hemorrhagic cystitis and nephrotoxicity in Wistar albino rats

Investigation of uroprotective effects of seed methanol extracts of Hypericum triquetrifolium Turra. on cyclophosphamide-induced bladder hemorrhagic cystitis and nephrotoxicity in Wistar albino rats

Optogenetic urothelial cell stimulation induces bladder contractions and pelvic nerve afferent firing

The mast cell stimulator compound 48/80 causes urothelium-dependent increases in murine urinary bladder contractility

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