Yoshiki Kurizaki

Relation between expression of α1-adrenoceptor mRNAs in bladder mucosa and urodynamic findings in men with lower urinary tract symptoms

Abstract Objective. To investigate the possible relationship between the bladder mucosal expression of α1-adrenoceptor (AR) mRNAs, storage symptoms and urodynamic findings in patients with lower urinary symptoms (LUTS) and benign prostatic obstruction (BPO). Material and methods. Mucosa was obtained from the posterior bladder wall from 20 patients with a diagnosis of LUTS and BPO undergoing prostatectomy. α1-AR subtype mRNA was quantified using competitive real-time reverse transcription–polymerase chain reaction. A preoperative video urodynamic study measured volumes for first desire to void (FDV) and strong desire to void (SDV). Patients were divided into group 1, with volumes for FDV ≤ 200 ml or SDV ≤ 300 ml, and group 2, with volumes FDV ≥ 201 ml and SDV ≥ 301 ml. Preoperative and postoperative international prostate symptom score (IPSS) and Overactive Bladder Symptom Score (OABSS) were evaluated. Results. The group 1 FDV (141.0 ± 13.5 ml) was significantly lower than that of group 2 (299.0 ± 48.1 ml). Similarly, the SDV for group 1 (247.0 ± 21.9 ml) was also significantly lower than for group 2 (444.0 ± 32.5 ml). There were no significant differences between groups 1 and 2 with respect to mucosal α1a- and α1b-AR mRNA levels. However, group 1 patients had significantly more α1d-mRNA than those in group 2. No relationship between the expression of α1-AR mRNAs and preoperative or postoperative OABSS or IPSS was detected. Conclusion. There was a relationship between the expression of α1d-AR mRNA in the bladder mucosa and storage-phase urodynamics in LUTS/BPO patients, suggesting a role of α1D-ARs in bladder sensation.

Functional roles of transient receptor potential melastatin 8 (TRPM8) channels in the cold stress‐induced detrusor overactivity pathways in conscious rats

We determined if transient receptor potential melastatin 8 (TRPM8) channels are involved in the detrusor overactivity induced by menthol, or exposure to low temperature (LT).

Stimulation of skin menthol receptors stimulates detrusor activity in conscious rats.

The Transient Receptor Potential Melastatin (TRPM)8 channel, activated by menthol and cool temperatures, has been proposed to be a cool receptor involved in mediation of the bladder response in the diagnostic ice water test. We examined the expression of TRPM8 in the rat skin and investigated if stimulation of skin menthol receptors by menthol can induce detrusor activity in conscious rats.

An extract (THC-002) of Ba-Wei-Die-Huang-Wan inhibits expression of tachykinins, and P2X3 and TRPV1 receptors, and inhibits ATP-induced detrusor overactivity in spontaneously hypertensive rats†‡

To investigate possible mechanisms of action of THC‐002 (HARNCARE®), a galenical produced from the traditional Chinese herbal mixture Ba‐Wei‐Die‐Huang‐Wan, which has been reported to improve lower urinary tract symptoms (LUTS) in patients.

Relationship between expression of β3-adrenoceptor mRNA in bladder mucosa and urodynamic findings in men with lower urinary tract symptoms.

To investigate the relationship between urinary bladder mucosal expression of β3‐adrenoceptor (AR) mRNA and urodynamic findings in patients with lower urinary tract symptoms and benign prostatic obstruction (BPO).

Relationship between Toe Temperature and Lower Urinary Tract Symptoms

Objective: Cold stress can elicit increases in urinary urgency and frequency. We determined if there was a relationship between finger and toe temperatures and lower urinary tract symptoms (LUTS).

The Relationship Between α1-Adrenergic Receptors and TRPM8 Channels in Detrusor Overactivity Induced by Cold Stress in Ovariectomized Rats

PURPOSE We studied whether cold stress induced detrusor overactivity in ovariectomized rats is associated with increased thermosensitive TRPM8 channel expression in the skin and whether the response could be inhibited by α1-adrenergic receptor blockade. MATERIALS AND METHODS A total of 24 Sprague-Dawley® rats at postnatal week 30 were randomly selected for ovariectomy (16) or sham ovariectomy (8). Five weeks later cystometric measurements of conscious, freely moving rats were made at room temperature (mean ± SEM 28C ± 2C) for 20 minutes. Eight ovariectomized rats were intravenously administered 1.0 mg/kg naftopidil. The other 8 ovariectomized and 8 sham operated rats were given naftopidil-free vehicle. Five minutes later they were transferred to a low temperature environment (mean 4C ± 2C) and micturition patterns were again recorded. TRPM8 channel expression in lumbar skin was estimated by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. RESULTS TRPM8 channel mRNA and protein in the skin of ovariectomized rats were significantly higher than in sham operated rats. At room temperature micturition parameters were similar in sham operated and ovariectomized rats. At low temperature sham operated and ovariectomized rats showed cold stress induced detrusor overactivity but increased micturition frequency and decreased bladder capacity were significantly greater in ovariectomized rats. Treatment of ovariectomized rats with naftopidil inhibited cold stress induced detrusor overactivity. CONCLUSIONS Cold stress induced detrusor overactivity in rats with decreased estrogen is associated with TRPM8 channel up-regulation in the skin and mediated by nerve pathways using α1-adrenergic receptors.

A galenical produced from Ba‐Wei‐Die‐Huang‐Wan (THC‐002) provides resistance to the cold stress‐induced detrusor overactivity in conscious rats

We determined if THC‐002, a galenical produced from Ba‐Wei‐Die‐Huang‐Wan, could increase skin temperature and inhibit detrusor overactivity induced by sudden whole body cooling. Further, we determined if THC‐002 could decrease expression of transient receptor potential melastatin 8 (TRPM8) channels associated with the cold responses.

Expression of 5-Hydroxytryptamine Receptors in Human Urinary Bladders with Benign Prostatic Hyperplasia

IntroductionThis study investigated the mRNA expression pattern and distribution of 5-hydroxytryptamine (5-HT) receptors 5-HT2A, 5-HT2B, 5-HT3A, 5-HT4, and 5-HT7 within the urothelium and detrusor of normal bladder tissue and in the urothelium of bladders from patients with benign prostatic hyperplasia (BPH).MethodsNormal urinary bladder specimens were obtained from 13 patients undergoing radical cystectomy due to bladder cancer (normal group) and BPH specimens were obtained from 27 benign prostatic obstruction patients receiving transurethral prostatectomy or retropubic prostatectomy. Receptor subtype mRNA expression was determined by real-time reverse transcription polymerase chain reaction on urothelium, detrusor, and whole mucosal preparations. Receptor distribution was determined by immunohistochemistry.ResultsIn normal tissues, expressions of 5-HT2B and 5-HT7 receptor mRNAs in the urothelium, detrusor, and whole mucosa were greater than the average expression for all receptor subtype mRNAs. 5-HT2B receptor protein was distributed in the apical urothelium and among the detrusor smooth muscle layers. In contrast, the 5-HT7 receptors were within the urothelium middle cell layers and detrusor smooth muscle cells. The expression pattern of each 5-HT receptor subtype mRNA within the BPH urothelium was similar to that in the normal urothelium. The expression level of 5-HT2A receptor mRNA in the BPH group was significantly lower than the normal group; however, the expressions of both 5-HT3A and 5-HT7 mRNAs were significantly higher. The expressions of both 5-HT2B and 5-HT4 mRNAs were not significantly different between the normal and BPH groups.ConclusionIn normal urinary bladders, the expressions of both 5-HT2B and 5-HT7 mRNAs were higher compared to the 5-HT2A, 5-HT3A, and 5-HT4 mRNAs. The distributions of 5-HT2B and 5-HT7 receptors were different in the urothelium and detrusor layers. The 5-HT3A and 5-HT7 receptor mRNAs in the BPH group were significantly higher compared to the normal urothelium, while the 5-HT2A mRNA was significantly lower.FundingAsahi Kasei Pharma Corporation.

Male lower urinary tract symptoms and α1D-adrenoceptors

Historically, α1‐adrenoceptors have been classified into three subtypes (α1A, α1B and α1D) that are widely distributed in various organs. Research on the α1D‐adrenoceptors in the bladder, urethra and prostate has focused on the relationship between expression levels and symptoms of bladder outlet obstruction, and the implications and functional roles of α1D‐adrenoceptors subtypes in these organs. The α1D‐adrenoceptor messenger ribonucleic acid and protein seem to be increased in obstructed bladders or small capacity bladders. In contrast, α1D‐adrenoceptor subtype knock‐out mice have been found to have a prolonged voiding interval. Interestingly, an α1D‐adrenoceptor antagonist was found to inhibit the facilitation of afferent nerve activity for the micturition reflex induced by intravesical infusion of acetic acid. Clinically, patients who felt urgency at low filling volumes and had a small bladder capacity were found to have more α1D‐adrenoceptor messenger ribonucleic acid in their bladder mucosa than patients who felt urgency at high filling volumes and had a large bladder capacity. An α1D‐adrenoceptor antagonist was found to increase the first desired volume and the maximum desired volume while decreasing detrusor overactivity in pressure flow studies. Thus, α1D‐adrenoceptors in the lower urinary tract might play an important role in the pathophysiology of lower urinary tract disorders.