EXPRESSION AND POSSIBLE FUNCTIONAL ROLE OF THE beta 3-ADRENOCEPTOR IN HUMAN AND RAT DETRUSOR MUSCLE

Fujimura, Takao; Tamura, Kouichi; Tsutsumi, Takeshi; Yamamoto, Takao; Nakamura, Keiko; Koibuchi, Yasushi; Kobayashi, Masakazu; Yamaguchi, Osamu

doi:10.1097/00005392-199902000-00099

Cited by 62 publications

(77 citation statements)

References 16 publications

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“…The β3-AR 8 is the predominant -AR in the human bladder [9][10][11] , and has recently become a therapeutic target for bladder storage symptoms. 12,13 However, the site(s) of action and mechanisms involved have not been…”

Section: Discussionmentioning

confidence: 99%

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

Kurizaki

Ishizuka

Imamura

et al. 2012

Neurourology and Urodynamics

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Aims: To investigate the relationship between urinary bladder mucosal expression of 3-adrenoceptor (AR) mRNA and urodynamic findings in patients with lower urinary tract symptoms and benign prostatic obstruction (BPO). Methods: During surgical prostate resection of 32 BPO patients, mucosal biopsies were collected and analyzed by reverse transcriptase polymerase chain reaction to determine the expression level of 3-AR mRNA.First desire to void (FDV) and strong desire to void (SDV), detrusor overactivity (DO), and bladder outlet obstruction (BOO) were measured preoperatively. Patients with FDVs <200 ml or SDVs <300 ml were assigned to the small capacity group (n=19). Patients with FDVs >201 ml and SDVs >301 ml were assigned to the large capacity group (n=13). The same patients with positive DO were also assigned to the DO+ group (n=11), and those with negative DO were assigned to the DO-group (n=21). Finally, patients whose position on the Schäfer nomogram was greater than degree V were assigned to the severe BOO group (n=17), while those with less than degree IV were assigned to the mild BOO group (n=15). Results: The expression level of 3-AR mRNA was similar in both bladder capacity groups and both DO groups.However, the expression level in the severe BOO group was significantly less than in the mild BOO group (p=0.043). Conclusions: The expression of bladder mucosal 3-AR mRNA was significantly decreased in patients with severe BOO, suggesting that β3-ARs might be affected by the degree of BOO.

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Section: Discussionmentioning

confidence: 99%

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

Kurizaki

Ishizuka

Imamura

et al. 2012

Neurourology and Urodynamics

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“…However, β3-ARs account for more than 95% of all β-AR mRNA in the human bladder and are thought to be the main β-ARs mediating human detrusor relaxation [Takeda et al 1999[Takeda et al , 2000Igawa et al 2010]. β3-ARs have been found to be highly and preferentially expressed on urinary bladder tissues, including the urothelium, interstitial cells, and detrusor smooth muscle [Andersson et al 2009;Andersson and Arner, 2004;Otsuka et al 2008;Limberg et al 2010;Fujimura et al 1999].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Mirabegron: a review of recent data and its prospects in the management of overactive bladder

Sacco

Bientinesi

2012

Therapeutic Advances in Urology

112

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Recent advances in the understanding of the physiopathology of OAB have driven a huge amount of basic and clinical research into novel pharmacological compounds. Among potential novel peripherally acting drugs, β3-adrenoceptor (AR) agonists appear very promising [Sacco et al. 2008]. Mirabegron (also known as YM178) is a novel, once-daily orally active, first-in-class, potent β 3-AR agonist [Takasu et al. 2007]. Regulatory applications for mirabegron are under review in several countries. In July 2011, mirabegron was granted marketing approval in Japan and was launched in September 2011. In June 2012 FDA also approved mirabegron (Myrbetriq, Astellas Pharma US, Inc.). Thereafter we reviewed clinical data on the safety and efficacy of mirabegron by searching English language full papers and abstracts in MEDLINE, ClinicalTrials.gov, controlled-trials.

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“…It has been shown that b 3 -AR agonists increase bladder capacity with no change in micturition pressure and residual volume. 108,[121][122][123][124] For example, Hicks et al 124 studied the effects of the selective b 3 -AR agonist GW427353 in the anesthetized dog and found that the drug evoked an increase in bladder capacity under conditions of acid-evoked bladder hyperactivity without affecting voiding. b 3 -AR selective agonists are currently being evaluated as potential treatment for OAB in humans.…”

Section: 105mentioning

confidence: 99%

Detrusor myocyte activity and afferent signaling

Andersson

2009

Neurourology and Urodynamics

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Aims: To discuss (1) mechanisms involved in the generation and control of myocyte contractions and consequent afferent nerve activity and (2) these mechanisms as targets for drugs aimed for treatment of overactive bladder (OAB) symptoms and detrusor overactivity (DO). Methods: Literature review of myocyte activation, bladder afferent nerves, mediators in the bladder, and translational aspects of the findings. Results: During bladder filling, there is normally no parasympathetic outflow from the spinal cord. Despite this, the bladder develops tone during filling and also exhibits non-synchronized local contractions and relaxations that are caused by a basal myogenic mechanical activity that may be reinforced by release of, for example, acetylcholine from non-neuronal and/or neuronal sources or local mediators, such as prostaglandins and endothelins. It is suggested that these spontaneous contractions are able to generate activity in afferent nerves (''afferent noise'') that may contribute to DO and OAB. Conclusions: Spontaneous bladder myocyte contractions and factors that are able to modulate them, as well as the consequent afferent nerve activity, may be targets for drugs meant for treatment of OAB/DO. Neurourol.

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EXPRESSION AND POSSIBLE FUNCTIONAL ROLE OF THE beta 3-ADRENOCEPTOR IN HUMAN AND RAT DETRUSOR MUSCLE

Abstract: These results suggest that beta3-AR agonists may be effective in the treatment of urinary frequency.

Cited by 62 publications

References 16 publications

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

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

Mirabegron: a review of recent data and its prospects in the management of overactive bladder

Detrusor myocyte activity and afferent signaling

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