Improvement of bladder storage function by α1‐blocker depends on the suppression of C‐fiber afferent activity in rats

Yokoyama, Osamu; Yusup, Anwar; Oyama, Nobuyuki; Aoki, Yoshitaka; Tanase, Kazuya; Matsuta, Yosuke; Miwa, Yoshiji; Akino, Hironobu

doi:10.1002/nau.20253

Cited by 40 publications

(29 citation statements)

References 33 publications

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“…15 In Japan, like tamsulosin, naftopidil is prescribed widely for patients with LUTS associated with BPH. 16 Several reports demonstrated that naftopidil improved bladder capacity and relaxed voiding via inhibition of afferent nerve activity, 17,18 and clinically improved not only obstructive voiding symptoms but also storage symptoms associated with BPH. 19,20 Kyprianou and Benning demonstrated that doxazosin and terazosin (quinazoline-derived a-1 adrenoceptor antagonists) had growth-inhibitory effects in human prostate cancer cell lines.…”

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confidence: 99%

Naftopidil, a selective α‐1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest

Kanda

Ishii

Ogura

et al. 2007

Intl Journal of Cancer

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a-1 adrenoceptor antagonists are generally prescribed for benign prostate hyperplasia with lower urinary tract symptoms. Naftopidil, a selective a-1 adrenoceptor antagonist, is frequently used in Japan because it has fewer side effects. Here we demonstrate for the first time that naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines. The concentrations causing 50% inhibition (IC50) of cancer cell growth were 22.2 6 4.0 lM in androgen-sensitive LNCaP cells and 33.2 6 1.1 lM in androgen-insensitive PC-3 cells. FACS analysis revealed that cell growth inhibition by naftopidil was due to the arrest of the G1 cell cycle. Expressions of p27 kip1 and p21 cip1 were significantly increased in LNCaP cells treated with naftopidil. In PC-3 cells, naftopidil induced p21 cip1 but not p27 kip1 . In vivo, oral administration of naftopidil to nude mice inhibited the growth of PC-3 tumors as compared to vehicle-treated controls. These results suggest that naftopidil may be useful in the chemoprevention of prostate cancer and the intervention of hormone refractory prostate cancer. ' 2007 Wiley-Liss, Inc.

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confidence: 99%

Naftopidil, a selective α‐1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest

Kanda

Ishii

Ogura

et al. 2007

Intl Journal of Cancer

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“…Several animal studies using rats and mice have demonstrated that the micturition reflex is facilitated by the α1D-AR subtype on urothelial cells 18,19. In addition, it has been demonstrated that naftopidil has an inhibitory effect on C-fiber afferents because the drug increases bladder capacity in rats with cerebral infarction, but not in C-fiber desensitized rats with cerebral infarction 20. Thus, naftopidil, with a higher affinity for the α1D-AR subtype, may contribute to improving detrusor overactivity through the blockade of the α1D-AR subtype not only in the prostate but also in nonprostatic organs.…”

Section: Rationale For Naftopidil Treatment Of Luts Suggestive Of Bphmentioning

confidence: 99%

Naftopidil for the treatment of urinary symptoms in patients with benign prostatic hyperplasia

Masumori¹

2011

TCRM

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Naftopidil, approved only in Japan, is an α1-adrenergic receptor antagonist (α1-blocker) used to treat lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Different from tamsulosin hydrochloride and silodosin, in that it has higher and extremely higher affinity respectively, for the α1A-adrenergic receptor subtype than for the α1D type, naftopidil has distinct characteristics because it has a three times greater affinity for the α1D-adrenergic receptor subtype than for the α1A subtype. Although well-designed large-scale randomized controlled studies are lacking and the optimal dosage of naftopidil is not always completely determined, previous reports from Japan have shown that naftopidil has superior efficacy to a placebo and comparable efficacy to other α1-blockers such as tamsulosin. On the other hand, the incidences of ejaculatory disorders and intraoperative floppy iris syndrome induced by naftopidil may be lower than for tamsulosin and silodosin having high affinity for the α1A-adrenergic receptor subtype. However, it remains unknown if the efficacy and safety of naftopidil in Japanese is applicable to white, black and Hispanic men having LUTS/BPH in western countries.

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“…Previous studies included factors within their methodologies that may limit the clinical relevance of their results. For example, many animal studies of afferent nerve activity from the LUTS have investigated the effect of a single‐dose of α 1 ‐AR antagonists 13,14 rather than the chronic administration of these agents, which would more closely approximate clinical conditions. Moreover, experiments without anesthesia are preferable to those with anesthesia, which could otherwise affect urinary function 15 .…”

Section: Introductionmentioning

confidence: 99%

Long‐term administration of prazosin improves bladder storage function: Results from a study in spontaneously hypertensive rats

et al. 2011

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Objectives:To investigate the effects of long-term administration of the a1-adrenoceptor antagonist prazosin on afferent inputs from the lower urinary tract (LUT). Methods: Twenty female spontaneously hypertensive rats (SHR) were randomized to receive a 4-week course of prazosin (0.12 mg/kg per day) or vehicle; 10 female Wistar-Kyoto (WKY) rats were given vehicle. Prazosin or vehicle was administered via an osmotic pump. The effect of prazosin on urodynamic parameters was determined by continuous cystometry in conscious animals. After cystometry, rats were killed and c-fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. Results: The bladder contraction interval was significantly shorter in untreated SHR compared with WKY rats (2.36 Ϯ 0 vs 4.27 Ϯ 0.12 min, respectively; P < 0.05) and cystometric capacity was decreased significantly in SHR compared with WKY rats. L6 spinal cord c-Fos expression was also significantly greater in SHR than WKY rats. The administration of prazosin significantly increased the micturition interval (4.07 Ϯ 0.58 min; P < 0.05) and bladder capacity, but it did not affect micturition pressure. In SHR, the number of c-Fos-positive neurons was significantly lower following the administration of prazosin compared with vehicle. Conclusions: Increased afferent input from the LUT may induce an increase in urinary frequency in SHR. Furthermore, long-term administration of prazosin can exert inhibitory effects on afferent pathways from the LUT during the storage phase. Reductions of afferent input can result in increased bladder capacity and increased micturition interval.

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Improvement of bladder storage function by α1‐blocker depends on the suppression of C‐fiber afferent activity in rats

Abstract: These results suggest that naftopidil has an inhibitory effect on C-fiber afferents in the lumbosacral spinal cord, improving BC during the storage phase.

Cited by 40 publications

References 33 publications

Naftopidil, a selective α‐1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest

Naftopidil, a selective α‐1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest

Naftopidil for the treatment of urinary symptoms in patients with benign prostatic hyperplasia

Long‐term administration of prazosin improves bladder storage function: Results from a study in spontaneously hypertensive rats

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