膀胱器官内淋巴管的研究

本文采用墨汁硝酸银水溶液局部动脉灌注方法,研究了鼠膀胱器官内淋巴管的构筑。所见结果表明:膀胱粘膜下层、肌层和外膜均存在淋巴管和毛细淋巴管,在粘膜下层淋巴管较丰富,三层淋巴管互相吻合,最后汇入外膜内的较粗大淋巴管内。在膀胱粘膜层仅见到丰富的毛细血管未观察到淋巴管或毛细淋巴管。     

盐酸丙哌维林对膀胱平滑肌收缩的影响(英文)

观察了盐酸丙哌维林 ( Pro)对离体豚鼠膀胱平滑肌自动节律性收缩和 KCl诱导离体豚鼠膀胱平滑肌收缩的影响 ;同时观察了 Pro对家犬在体膀胱自动节律性收缩的影响 .Pro在 1 ,1 0 μmol· L-1浓度时 ,对离体豚鼠膀胱平滑肌自动节律性活动具有兴奋作用 ,可使自动节律性收缩频率增加 ,幅度加大 ;在 1 0 0μmol· L-1浓度时则表现为抑制作用 ,可完全抑制豚鼠膀胱平滑肌的自动节律性收缩 ,同时可使平滑肌松弛 ,基础张力降低 .Pro对 KCl引起的豚鼠离体膀胱平滑肌的收缩具有明显的抑制作用 ,在 1 ,1 0 ,1 0 0 μmol· L-1浓度时对 KCl诱导豚鼠离体膀胱平滑肌收缩的抑制率分别为 ( 7.4±6.5) % ,( 31 .3± 1 2 .8) % ,( 68.4± 7.1 ) % ,其 IC50 为( 2 5.2± 4.7) μmol·L-1.十二指肠给 Pro对在体家犬膀胱自动节律性收缩具有明显的抑制作用 ,60 ,30mg· kg-1可明显降低膀胱自动节律性收缩频率和幅度且具有剂量依赖性 ,与药前比有显著性差异 ,60 mg· kg-1药后 1 0 min即可起效 ,药效可持续 90min,Pro在上述剂量下对血压 ,心率无明显影响 .本实验结果提示 Pro在低剂量时对离体膀胱自动节律性收缩具有一定的兴奋作用 ,在高剂量时则表现为明显的抑制作用 ;Pro对 KCl诱导的豚鼠离体膀胱平滑肌收缩和膀胱扩张诱导的家?     

钩藤碱对大鼠膀胱逼尿肌舒缩作用的影响

目的观察钩藤碱(rhynchophylline,Rhy)对离体大鼠逼尿肌的作用并探讨其作用机制。方法采用逼尿肌体外张力实验法检测Rhy对大鼠逼尿肌L-型钙通道(ICa-L)及大电导钙离子激活钾离子通道(BKCa)作用。以维拉帕米为对照观察膀胱逼尿肌肌条的收缩及对乙酰胆碱(ACh)依赖细胞内、外钙所致肌条收缩程度的拮抗作用。结果 Rhy和BKCa激动剂NS1619作用相似,亲和力指数(pD2)分别为4.78±0.17、4.53±0.22;BKCa拮抗剂iberiotoxin能竞争性拮抗Rhy,使Rhy累积量效曲线平行右移,拮抗参数(pA2)为7.27±0.16;当Rhy浓度为1~20μmo.lL-1时,使CaCl2累积量效曲线非平行右移,最大反应降低,呈非竞争性拮抗。结论 Rhy通过离子通道(阻滞ICa-L、激活BKCa)抑制膀胱逼尿肌收缩。低浓度(10μmol.L-1)Rhy仅对细胞内钙引起的肌条收缩有抑制作用,而对细胞外钙所致的肌条收缩无影响;随着浓度的增高,Rhy对细胞内、外钙引起的肌条收缩均有抑制作用,且抑制作用逐渐增加。     

The contractile effect of bombesin on the rat isolated urinary bladder

We have investigated and compared the myotropic effects of bombesin (BB) and carbachol (C) in the rat isolated urinary bladder. BB (0.5 x 10(-9) to 0.5 x 10(-5) M) and C (2.7 x 10(-8) to 5.4 x 10(-5) M) were found to produce dose-dependent increases of the basal tone of the rat detrusor muscle. The maximal contraction produced by C was about 4 times greater than that elicited by BB or substance P (SP). However, the threshold concentrations of BB and SP required to stimulate the detrusor muscle were much lower than those of C. The pD2 (-log ED50) values of BB, SP and C were respectively 7.63, 7.05 and 5.8. The tissues exposed to BB relaxed more slowly after washout than those challenged with C or SP. The contractile effects of medium range concentrations of BB were not affected by pretreating the tissues with tetrodotoxin, atropine, antihistaminics, indomethacin, alpha- and beta-adrenergic blockers, methysergide or 8-leucine-angiotensin II. Tissues desensitized with high concentrations of bradykinin maintained their sensitivity to BB. The result suggest that the contractile effect of BB on the rat isolated urinary bladder is likely to be the result of a direct effect on the smooth muscle cells.     

Effects of chlorogenic acid on carbachol-induced contraction of mouse urinary bladder

Chlorogenic acid (CGA) is a polyphenol found in coffee and medicinal herbs such as Lonicera japonica. In this study, the effect of CGA-induced relaxation on carbachol (CCh)-induced contraction of mouse urinary bladder was investigated. CGA (30–300 μg/ml) inhibited CCh- or U46619-induced contraction in a concentration-dependent manner. SQ22536 (adenylyl cyclase inhibitor) recovered CGA-induced relaxation of CCh-induced contraction; however, ODQ (guanylyl cyclase inhibitor) did not have the same effect. In addition, 3-isobutyl-1-methylxanthine (IBMX) enhanced CGA-induced relaxation; however, forskolin or sodium nitroprusside did not have the same effect. Moreover, Ro 20–1724, a selective phosphodiesterase (PDE) 4 inhibitor, enhanced CGA-induced relaxation, but vardenafil, a selective PDE5 inhibitor, did not have the same effect. In the presence of CCh, CGA increased cyclic adenosine monophosphate (cAMP) level, whereas SQ22536 inhibited the increase of cAMP levels. Moreover, higher cAMP levels were obtained with CGA plus IBMX treatment than the total cAMP levels obtained with separate CGA and IBMX treatments. In conclusion, these results suggest that CGA inhibited CCh-induced contraction of mouse urinary bladder by partly increasing cAMP levels via adenylyl cyclase activation.     

盐酸丙哌维林对豚鼠离体膀胱平滑肌条的钙拮抗作用

目的　研究盐酸丙哌维林 (P 4)对豚鼠离体膀胱平滑肌条的钙拮抗作用及作用机制。方法　采用离体平滑肌条浴槽实验方法 ,以维拉帕米为对照 ,测定P 4对CaCl2 和组胺 (His)所致离体膀胱平滑肌条的收缩及对乙酰胆碱 (ACh)所致膀胱平滑肌依赖细胞内钙、外钙收缩的影响。结果　P 41～ 1 0 0 μmol·L- 1 使CaCl2 累积量效曲线非平行右移 ,最大反应降低 ,pD2 ′为 4 73± 0 1 4。P 41 μmol·L- 1 使His量效曲线平行右移 ,最大效应不变 ,pA2 为 5 44± 0 1 4 ;1 0～ 1 0 0μmol·L- 1 使His量效曲线非平行右移 ,最大效应降低 ,pD2 ′为 4 71± 0 1 0。P 41、1 0和 1 0 0 μmol·L- 1 对ACh所致依赖细胞内钙收缩的抑制率分别为 45 77%± 6 54 %、86 2 6 %± 5 59%和 90 55 %± 3 1 1 % ,对依赖细胞外钙收缩的抑制率分别为 7 30 %± 2 89%、49 1 6 %± 6 0 9%和 88 2 5 %±3 70 %。结论　P 4低浓度时竞争性拮抗His所致膀胱平滑肌条的收缩反应 ,明显抑制膀胱平滑肌条依赖细胞内钙释放的收缩反应 ;高浓度时非竞争性拮抗His和CaCl2 所致膀胱平滑肌条的收缩反应 ,明显抑制膀胱平滑肌条依赖细胞内钙释放和外钙经钙通道内流所致收缩反应     

Neurogenic and non-neurogenic responses in the urinary bladder of hibernating hamster

1. Purinergic and cholinergic components of parasympathetic neurotransmission and contractile responses to exogenous α,β-methylene ATP, acetylcholine, substance K, substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide and capsaicin have been investigated in the urinary bladder of hibernating hamsters (4 weeks), cold exposed (4 weeks) and age-matched controls.
2. Electrical field stimulation (EFS) evoked increased frequency-dependent contractions in the detrusor strips from hibernating hamsters compared with those obtained from cold-exposed and age-matched animals. Tetrodotoxin (10⁻⁶ M) completely blocked the frequency-dependent contractions in all groups.
3. The purinergic component of the parasympathetic neurotransmission was not affected in hibernating and cold-exposed animals while the cholinergic component was increased with respect to age-matched animals. The neurogenic response to EFS, still present after incubation with atropine (10⁻⁶ M) and suramin (10⁻⁴ M), was attenuated by indomethacin (10⁻⁶ M) and blocked by tetrodotoxin (10⁻⁶ M).
4. Exogenous administration of α,β-methylene ATP elicited a significantly reduced contraction in strips from hibernating and cold-exposed hamsters relative to age-matched animals. The contractile response to exogenous acetylcholine was greater in the detrusors from hibernating hamsters than in cold-exposed and age-matched animals. Substance K elicited reduced contractions in preparations from hibernating animals compared with cold-exposed and control animals. Calcitonin gene-related peptide, vasoactive intestinal polypeptide, substance P and capsaicin did not elicit any relaxant or contractile response either at resting tone or in carbachol (5×10⁻⁷ M)-precontracted tissues.
5. In summary, our findings indicate that 4 weeks of hibernation can significantly increase neurogenic responses in the hamster urinary bladder. This appears to be due to an increase in postjunctional responses to acetylcholine. In contrast, there was a decrease of the postjunctional responses to the parasympathetic cotransmitter ATP and also to the sensory-motor neurotransmitter substance K.

     

膀胱癌肉瘤诊治2例报告并文献复习

目的结合文献复习,提高膀胱癌肉瘤的诊治水平。方法回顾分析2例膀胱癌肉瘤患者的临床和病理资料。男女各1例,均以无痛性肉眼血尿为主要症状,B超或CT提示膀胱占位,膀胱镜下见膀胱内肿物,活检病理2例均提示移行细胞癌。结果2例均行膀胱部分切除,术后病理均为膀胱癌肉瘤,显微镜下主要由高分化移行细胞癌和肉瘤成分组成。免疫组化显示：CK及Vimentin反应均为阳性。结论诊断依赖病理及免疫组化检查,治疗以根治性手术为主,预后不良。     

叶绿素衍生物在犬膀胱粘膜内代谢的研究

目的：为了了解叶绿素衍生物（ＣＰＤ４）口服后在膀胱粘膜内含量变化的状况，以便为临床应用提供实验依据。方法：１３条实验犬分为３个不同剂量组，应用荧光检测法作服药后不同时段膀胱粘膜ＣＰＤ４含量的测定。结果：ＣＰＤ４用于实验犬的合适剂量是１００ｍｇ／ｋｇ，明显低于此值将显著影响组织的吸收，从而降低光动力作用。在禁食组中，组织内吸收的最高峰值出现在服药后２ｈ，而进食组却推迟出现在服药后６￣１２ｈ。结论：为     

E-cad在膀胱癌中的表达及意义

目的：探讨E-cad在膀胱癌中的表达及意义。方法：通过免疫组织化学法和RT-PCR法检测E-cad在膀胱癌和正常膀胱组织中的表达。结果：免疫组织化学方法对正常膀胱组织和膀胱癌组织中的E-cad进行了检测,发现E-cad蛋白在膀胱癌组织中的阳性表达率为32.39%（23/71）,正常膀胱黏膜组织表达的阳性率为100%,E-cad在膀胱癌组织中的表达明显低于正常组织。RT-PCR法从基因水平检测正常膀胱组织和膀胱癌组织中E-cad的表达,E-cad在正常膀胱组织所得光密度值为0.940±0.052,膀胱癌组织的光密度值为0.754±0.044,经统计学分析,E-cad在膀胱癌组织中的表达与正常膀胱组织表达相比差异有显著性（t=11.142,P〈0.01）。结论：无论是在蛋白还是基因水平上,E-cad在膀胱癌组织中的表达低于正常膀胱组织的表达。     

Acid secretion in urinary bladder of rats subjected to gastrocystoplasty

Urinary bladder augmentation with a segment of the stomach, i.e., gastrocystoplasty, has been used to improve capacity and compliance in patients with bladder dysfunction. In the present study, rats were subjected to gastrocystoplasty (using the oxyntic segment) with or without fundectomy (removal of the oxyntic part of stomach), and the acid secretion in the augmented bladder was measured. In freely fed rats, the pH values were neutral and not significantly decreased in the rats subjected to gastrocystoplasty with or without fundectomy compared to controls (no operation or sham operation). In response to food intake after being fasted, the rats subjected to gastocystoplasty + fundectomy produced significant amounts of acid. Immunohistochemical examination revealed that the ECL cells and parietal cells seemed to be normal in rats with gastrocystoplasty alone, and that micronodules of ECL appeared to develop in rats with gastrocystoplasty + fundectomy. We suggest that the rats subjected to gastrocystoplasty + fundectomy are capable of producing acid secretion in the bladder, probably due to the secretagogue and trophic effects of gastrin on the ECL cells in the segment of the oxyntic mucosal segment of the bladder.     

Effects of co-administration of antioxidants and arsenicals on the rat urinary bladder epithelium.

Oxidative stress has been increasingly recognized as a possible mechanism in the toxicity and carcinogenicity of various chemicals, including arsenic. Therefore, treatment with antioxidants may afford a protective effect against arsenic-induced cytotoxicity and carcinogenesis. Dimethylarsinic acid (DMAV) has been shown to be a bladder carcinogen in rats when administered at high doses (100 ppm) in the diet or in the drinking water. The main purpose of the present study was to evaluate the effects of co-administration of antioxidants with arsenicals on the rat urinary bladder epithelium in vitro and in vivo. In a previous experiment, treatment with 1000 ppm melatonin for two weeks did not inhibit cell proliferation induced in the rat urothelium by 100 ppm DMAV. In the current study, we examined the effects of five antioxidants that act via different mechanisms, on the in vitro cytotoxicity of various arsenicals, for the purpose of determining which antioxidants might have protective effects against arsenic-induced cytotoxicity. The antioxidants that inhibited cytotoxicity in vitro were then studied also in vivo. Melatonin showed slight inhibition of the cytotoxicity of arsenite, but had no effect on the other arsenicals. N-acetylcysteine (NAC) inhibited the cytotoxicity of monomethylarsonous acid (MMAIII), DMAV, dimethylarsinous acid (DMAIII), and trimethylarsine oxide (TMAO). Vitamin C inhibited cytotoxicity induced by arsenate, arsenite, MMAIII) and DMAIII. Tiron and Trolox had no effect on the cytotoxicity of any arsenical. The in vitro inhibitory effects of NAC and vitamin C on DMAV and on DMAIII, suggested that these antioxidants might afford preventive effects on DMAV-induced bladder cytotoxicity and carcinogenesis in rats. To test this hypothesis, a 10-week rat bioassay was conducted. Melatonin was also included to clarify the results of the previous two-week experiment. The sodium salt of vitamin C (Na-Asc), but not melatonin or NAC, inhibited the proliferative effects of DMAV on the bladder epithelium in rats. These results suggest that oxidative stress is at least in part involved in DMAV-induced rat bladder toxicity and proliferation, and therefore, vitamin C may afford inhibitory effects in DMAV-induced bladder carcinogenesis in rats. Microarray analysis of DMAV-responsive genes revealed that DMAV did not have a consistent modifying effect on gene expression in the rat bladder epithelium, suggesting that proteins and/or lipids may be the targets of damage by DMAV-induced oxidative stress.     

Subchronic urinary bladder effects of muraglitazar in male rats.

Muraglitazar, a PPARalpha/gamma dual agonist, was dosed orally to rats once daily for 13 weeks to evaluate urinary and urothelial changes of potential relevance to urinary bladder tumorigenesis. Groups of 17 young or aged rats per sex were fed a normal or 1% NH4Cl-supplemented diet and were dosed with 0, 1, or 50 mg/kg muraglitazar. Lithogenic ions and sediment were profiled from freshly voided urine samples collected 24 h after dosing, and drug exposures were measured. Urinary citrate, oxalate, and epidermal growth factor (EGF) were assayed from 18-h urine collections. Urothelium was assessed by light microscopy, scanning electron microscopy, and BrdU and TUNEL immunohistochemistry. When fed a normal diet, urine pH was higher in males (above 6.5). Urine volume/body weight was greater in females. Urine soluble/total calcium and magnesium and phosphorus/creatinine ratios were lower in male rats fed a normal diet. Urine citrate levels were decreased and oxalate was increased in young male rats treated with 50 mg/kg muraglitazar compared to age/sex/diet-matched controls. No changes in urine sediment were detected 24 h after dosing. In young male rats treated with 50 mg/kg on normal diet, multifocal urothelial necrosis and proliferation were observed, whereas urothelial apoptosis and urine EGF levels were unchanged compared to age/sex/diet-matched controls. Urothelial necrosis and proliferation were not correlated to systemic or urinary drug exposures and were prevented by dietary acidification. These data suggest that muraglitazar-associated changes in urine composition predispose to urothelial cytotoxicity and proliferation in the urinary bladder of young male rats and that urine sediment must be profiled at multiple daily timepoints to fully qualify drug-induced changes in urine composition.     

The effect of troxypyrrolidinium,a choline uptake inhibitor,on the excitatory innervation of the rat urinary bladder

Troxypyrrolidinium, a choline uptake inhibitor, reduced but failed to abolish responses of the rat urinary bladder to electrical stimulation at 1–100 Hz although it reduced acetylcholine output during stimulation at 10 Hz to a level similar to that of spontaneous release. Inhibition of the response to stimulation was more complete at faster rates of stimulation and was partially reversed by choline. Troxypyrrolidinium produced a greater inhibition of the ‘tonic’ component of the response to electrical stimulation than of the ‘phasic’ component. Hemicholinium-3 or hyoscine produced a similar selective effect on the ‘tonic’ component. Hemicholinium-3 also reduced acetylcholine output during electrical stimulation to a similar extent as troxypyrrolidinium but hyoscine increased transmitter output. The results support the concept of a second transmitter in the excitatory innervation of the bladder.     

Effect of nefiracetam, a neurotransmission enhancer, on primary uroepithelial cells of the canine urinary bladder.

Repeated oral treatment of dogs with a high dose of nefiracetam is reported to induce hemorrhagic lesions in the urinary bladder. To delineate its pathogenesis, we established the primary culture of uroepithelial cells of the canine urinary bladder, and then explored the effect of nefiracetam on the cultured cells. Uroepithelial cells scraped from the connective tissues of the urinary bladder of naive dogs were suspended in the minimum essential medium containing dispase, and then resuspended in the keratinocyte medium to be 6.0-7.0 x 10(5) cells/ml. Afterward, they were added to an apical chamber with a 12-mm transwell filter, cultured for three days, and recultured in the keratinocyte medium containing 1 mM CaCl(2) for 20 days. Microscopically, these cultured cells consisted of three cell layers with high transepithelial electric resistance (TER; > 10,000 ohm-cm(2)). Immunofluorescence observations revealed ZO-1 and E-cadherin bands, and electron microscopic examinations displayed the superficial cells with the assembly of tight junctions. When the effect of nefiracetam and its five main metabolites (M-3, M-10, M-11, M-18, and M-20) on TER and the ZO-1 band was assessed using cultured cells, only M-18 significantly reduced TER in the coculture for 48 h or more. Both M-10 and M-18 exhibited a deformation of uroepithelial cells and a slight reduction of the ZO-1 band from 120 h later. In conclusion, this culture system possesses both functional and morphological features of the uroepithelium reflected in vivo, and M-18 may play a pivotal role in the impairment of uroepithelial cells, leading to the onset of the urinary bladder lesion in dogs due to nefiracetam.     

Animal models of urinary bladder cancer and their application to novel drug discovery

Introduction: Urinary bladder cancer is a major human malignancy that afflicts millions of people worldwide every year. Urinary bladder cancer is usually superficial at presentation in 70 – 80% of patients. In these cases, a simple transurethral resection is adequate for removing the tumor. However, some patients experience recurrence or even tumor progression. In another 20 – 30% of patients, muscle-invasive carcinoma is diagnosed. Despite all the developments in this area, even today, the options for treatment of urinary bladder cancer remain inadequate. The search for the mechanisms involved in human urinary bladder cancer and for new and improved treatment methods has led to the development of many experimental models using laboratory animals over the past 40 years.

Areas covered: In this review, the authors provide a concise overview of the animal models used to study urinary bladder cancer. Furthermore, the authors discuss their advantages and disadvantages with regard to the search for new therapeutic approaches.

Expert opinion: The use of urinary bladder cancer models for understanding the mechanisms involved in tumors' response to new treatments is an important step in the drug discovery process. However, the authors believe that it will be necessary to develop our knowledge and understanding of the molecular processes underlying urothelial chemical carcinogenesis for us to better evaluate the efficacy of novel therapeutics.     

Oxybutynin for treatment of urge urinary incontinence and overactive bladder: an updated review

Urge urinary incontinence (UUI) and overactive bladder are common conditions often associated with profound impairment of the health and quality of life of the patient. Antimuscarinic medications have been the mainstay of treatment for these disorders. Oxybutynin hydrochloride, one of the most widely used antimuscarinic agents, has attracted considerable interest from both clinicians and pharmacologists over the last three decades. Although efficacy of this drug has been proven to be high, its use is limited by antimuscarinic adverse effects, possibly related to its active metabolite N-desethyloxybutynin (N-DEO). The extended-release form of oxybutynin uses a push-pull osmotic release system which has significantly improved its tolerability and safety profile. A transdermal transport system has also been developed, bypassing the first-pass metabolism in the liver and gut. This system is associated with significant reduction in the production of the primary metabolite and additional improvement in the tolerability profile of the drug. Intravesical instillation of oxybutynin has been reported although the efficacy and safety of this delivery system has yet to be determined. This article comprehensively reviews the contemporary literature on the pharmacology, clinical efficacy and adverse reactions of oxybutynin in its various delivery forms, and compares them to other frequently used medications for UUI and overactive bladder.     

Subchronic urinary bladder toxicity evaluation of N‐Nitrosodiphenylamine in Fischer 344 rats

Female Fischer 344 (F344) rats were exposed to N‐nitrosodiphenylamine (NDPA) by dietary feed at concentrations of 0, 250, 1000, 2000, 3000 or 4000 ppm for 5 days, 2, 4 and 13 weeks duration. Endpoints evaluated included clinical observations, body weights, urinary bladder weights, blood NDPA, gross pathology and urinary bladder histopathology. There were no NDPA exposure‐related clinical signs of toxicity. The mean body weight decreased 3% to 5% compared with the control in the 4000 ppm group during study weeks 2 through to 13. Statistically significant increases in urinary bladder weight were observed as early as after 5 days exposure and were concentration dependent at ≥ 3000 ppm. NDPA‐related urinary bladder microscopic alterations consisted of mixed cell infiltrates, increased mitosis, increased necrosis of epithelial cells, diffuse and/or nodular transitional epithelial hyperplasia and squamous metaplasia of transitional epithelium. These changes affected only rats exposed to NDPA concentrations ≥ 2000 ppm. Blood NDPA concentrations were negligible in animals exposed to ≤ 1000 ppm and ranged from 0.12 to 0.19 µg ml^–1 in rats of the ≥ 2000 ppm groups at the 5 days and 2 weeks time points. A no observable adverse effect level (NOAEL) of 1000 ppm NDPA (60 mg kg^–1 day^–1) was selected based on the absence of urinary bladder histopathology. Copyright © 2012 John Wiley & Sons, Ltd.     

Dual modulation of urinary bladder activity and urine flow by prostanoid EP3 receptors in the conscious rat

Background and purpose:

Cyclooxygenase inhibitors function to reduce levels of prostaglandin E₂ (PGE₂) and are broadly efficacious in models of bladder overactivity. We therefore investigated a regulation of urinary bladder function in conscious rats by modulation of the EP₃ receptor for PGE₂.

Experimental approach:

The activity of the EP₃ receptor agonist GR63799X, and EP₃ receptor antagonists, CM9 and DG041, at recombinant EP₃ receptors was evaluated in vitro. In vivo, intraduodenal dosing during conscious, continuous-filling cystometry of spontaneously hypertensive rats was utilized to determine the urodynamic effect of EP₃ receptor modulation.

Key results:

GR63799X dose-dependently (0.001–1 mg·kg⁻¹) reduced bladder capacity, as indicated by a reduction in both the micturition interval and volume of urine per void. In contrast, CM9 (10 and 30 mg·kg⁻¹) and DG041 (30 mg·kg⁻¹) enhanced bladder capacity, as indicated by significantly longer micturition intervals and larger void volumes. CM9 and DG041 inhibited the responses to GR63799X supporting the in vivo activity of these pharmacological agents at the EP₃ receptor. In addition to its effect on bladder capacity, GR63799X increased endogenous urine production. Intra-arterial infusion of saline mimicked the enhancement of urine flow observed with GR63799X, and the response was inhibited by CM9.

Conclusions and implications:

These data support the EP₃ receptor as a modulator of urinary bladder activity in the conscious rat, and in addition, indicate a role for EP₃ receptor activity in regulating urine flow.