Hidenori Zakoji

Differential Expression Profile of Cold (TRPA1) and Cool (TRPM8) Receptors in Human Urogenital Organs

OBJECTIVES To examine the expressions of transient receptor potential (TRP) channel A1 and TRPM8 in the human urogenital organs (urinary bladder and prostate) and how these expressions change in association with bladder outlet obstruction (BOO) or benign prostatic hyperplasia (BPH). In addition to TRPM8, a cool receptor, TRPA1 is recently recognized as a cold receptor. TRPA1 is also a candidate for mechanosensor and/or nociceptor. METHODS Urinary bladder mucosa and muscular layer were taken from 9 controls and 9 patients with BOO. Prostatic specimens were obtained from 5 controls and 6 patients with BPH. Expressions of TRPA1 and TRPM8 messenger RNAs (mRNAs) were quantified by real-time revere transcriptase-polymerase chain reaction. Localization of TRPA1 protein was explored with immunohistochemistry. RESULTS The expression levels of TRPA1 mRNA in the bladder mucosa, bladder muscular layer, and prostate were in the ratio of 639:1:16. TRPA1 mRNA in the bladder mucosa with BOO was significantly upregulated to 2.32 times of control. TRPA1 protein was localized in the epithelial cells of both urinary bladder and prostate gland. The expression of TRPM8 mRNA in the prostate was much higher than that in the bladder mucosa (3024:1), but was not found in the bladder muscle layer. BPH or BOO did not significantly affect the expression of TRPM8. CONCLUSIONS TRPA1 and TRPM8 were differentially expressed in the human urinary bladder and prostate. TRPA1 in the bladder epithelium might be involved in the bladder sensory transduction and the induction process of overactive bladder by BOO.

Sex differences in the expression profile of acid‐sensing ion channels in the mouse urinary bladder: a possible involvement in irritative bladder symptoms

To investigate the expressions and sex differences of acid‐sensitive ion channels (i.e. ASIC and transient receptor potential channel V1, TRPV1; both key receptors for extracellular protons that might underlie the acid‐evoked pain perception) and other nociceptive ion channels in the mouse bladder.

Roles of mechanosensitive ion channels in bladder sensory transduction and overactive bladder

Abstract:  In the storage phase, mechanical stretch stimulates bladder afferents. These signals generate sensations and trigger voiding responses, however the precise mechanisms by which mechanical stimuli excite bladder afferents are yet to be explored. For mechanosensory transduction, the presence of mechanosensors is essential in the peripheral sensory systems including sensory nerve endings, urothelium and others. There is increasing evidence that mechanosensitive ion channels, such as degenerin/epithelial Na+ channel (ENaC) and transient receptor potential (TRP) channel families, play key roles in the mechanosensory transduction of the urinary bladder. Pharmacological interventions targeting mechanosensitive ion channels may provide a new strategy for the treatment of bladder dysfunction.

Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

Sex-related differences in lower urinary tract (LUT) activity responding to intravesical infusion of diluted acetic acid (A/A, pH 3.0) were investigated during cystometrograms in decerebrate unanesthetized mice. A/A produced a decrease of intercontraction intervals in both female and male animals, and the extent of the decrease in male mice was much less than in female mice [19 +/- 5% (P = 0.03) vs. 65 +/- 5% (P = 0.03); n = 6 for each], exhibiting a marked difference between the two groups in response to acid irritation of the LUT (P = 0.002). A/A reduced maximal voiding pressure (MVP) (19 +/- 4%, P = 0.03) but had no effect on pressure threshold for inducing voiding contraction (PT) (P = 0.56) in females, whereas A/A did not change MVP (P = 1.00) but increased PT (16 +/- 4%, P = 0.03) in males. A/A decreased bladder compliances of female and male mice in a similar fashion (44 +/- 10% vs. 24 +/- 7%, P = 0.03 for each). In male mice, A/A produced persistent dribbling of fluid after voiding contraction phase, which was virtually not seen in females. The present study demonstrates the differences between female and male mice in response to noxious stimulation in the LUT: the female bladder is more sensitive to the acid irritation, while the male urethra is more irritable to the noxious stimulus. Identification of mechanisms underlying sex-specific characteristics might be helpful for elucidating pathogenesis of painful bladder syndrome.

Bladder outlet obstruction induced expression of prostaglandin E2 receptor subtype EP4 in the rat bladder: a possible counteractive mechanism against detrusor overactivity.

PURPOSE Prostaglandins have been implicated as endogenous modulators of bladder function under physiological and pathological conditions. We examined how the expression of each EP receptor subtype changed in association with bladder outlet obstruction and focused on the functional role of EP4 receptor subtype in the bladder with outlet obstruction. MATERIALS AND METHODS We assessed the gene expression of EP receptor subtypes by reverse transcriptase-polymerase chain reaction. EP4 protein localization was determined by immunohistochemistry. The effect of the selective EP4 agonist ONO-AE1-329 on 50 mM KCl induced contraction of rat bladder strips was examined in vitro. Continuous infusion cystometrograms were done to examine the effect of intravesical perfusion of ONO-AE1-329 on the micturition reflex in urethane anesthetized rats. RESULTS EP4 receptor genes were largely expressed in bladders with outlet obstruction but absent in controls. EP4 receptor proteins were clearly detected in obstructed bladder detrusor smooth muscle and epithelium. ONO-AE1-329 (100 μM) significantly relaxed KCl induced contraction of bladder strips from rats with bladder outlet obstruction. A significant correlation was found between the relaxant effect of ONO-AE1-329 and whole bladder weight. In rats with bladder outlet obstruction intravesical infusion of 10 μM ONO-AE1-329 significantly increased bladder capacity without changing micturition pressure while it had no effect in controls. CONCLUSIONS Activation of the EP4 receptors expressed in bladders with outlet obstruction may suppress detrusor muscle contraction and afferent activity. This might be a compensatory mechanism to counteract the deterioration of storage function in bladders with outlet obstruction.

Decreased expression of G protein‐coupled receptor kinases in the detrusor smooth muscle of human urinary bladder with outlet obstruction

Aim: We examine the expression of mRNA of G protein‐coupled receptor kinase (GRK) subtypes and muscarinic acetylcholine receptor (M) subtypes in the detrusor smooth muscle of the human urinary bladder. Furthermore, we confirm the presence and the localization of GRK proteins in the detrusor smooth muscle of the obstructed bladder in comparison with the control bladder.

Hemorrhagic Renal Angiomyolipoma in Pregnancy Effectively Managed by Immediate Cesarean Section and Elective Transcatheter Arterial Embolization: A Case Report

Abstract Renal angiomyolipoma (AML) is a benign renal tumor with a risk of rupture in intratumoral aneurysms. Although renal AML in pregnancy is rare, risk of rupture is greater. Management for AML and childbirth is important during pregnancy; however, it is undefined yet. We present a case of hemorrhagic angiomyolipoma in pregnancy that is effectively managed by immediate cesarean section and elective transcatheter arterial embolization.

Contralateral Adrenal Metastasis of Renal Cell Carcinoma Arising From a Horseshoe Kidney: An Initial Case Report.

A 71-year-old woman with a right adrenal mass detected by computed tomography was referred to our institution. Before 33 months, she had undergone a radical heminephrectomy for an 11-cm renal cell carcinoma (RCC) in the left moiety of a horseshoe kidney. The adrenal tumor was diagnosed as the metastasis of RCC. The tumor was subsequently removed in a laparoscopic adrenalectomy by a retroperitoneal approach. Pathologic examination revealed the mass to be the adrenal metastasis of RCC. To our knowledge, this is the initial report of a laparoscopic adrenalectomy for the adrenal metastasis of renal cell carcinoma arising from a horseshoe kidney.

Postrenal Failure due to Urinary Stones Associated with Acute Viral Gastroenteritis: Three Case Reports

Acute gastroenteritis with viral infection in infants causes severe diarrhea and often results in acute renal failure due to severe dehydration. However, a viral infection, particularly rotavirus, rarely induces postrenal failure due to bilateral stones in infants. Herein, we report three cases of postrenal failure in infants due to bilateral ureteral stones induced by acute gastroenteritis with rotavirus. Following immediately nephrostomy, chemical dissolution therapy succeeded to treat postrenal failure. Immediate nephrostomy for the release of upper urinary tract obstruction combined with urinary alkalization as a chemical dissolution therapy should be considered in such cases.

The Artificial Urinary Sphincter Infection that Occurred 10 Years Laterfrom Implantation

An 82-year-old diabetic man with AMS 800™ in the bulbar urethra was referred to our hospital with lower abdominal pain and swelling. He underwent open sigmoidectomy with indwelling of urethral catheter a month ago. Abdominal and pelvic CT showed the inflammatory change around the device. Urethroscopy revealed urethral erosion and bulge of cuff into the lumen of urethra. Immediately, he was treated with a course of antibiotics administration, however, the device tube became exposed on the outside of scrotum skin 6 months later. We have removed the device except cuff and a part of tube because it was thought to be difficult to separate it from the urethra. The infection rate of AMS800TM is known to be 3.3~27.8%, mostly infection has occurred in 2 years. It was a rare case of infection that occurred 10 years later from implantation in association with abdominal surgery.