The effect of bladder outlet obstruction on α<sub>1</sub>‐ and β‐adrenoceptor expression and function

Barendrecht, Maurits M.; Frazier, Elfaridah P.; Vrydag, Wim; Alewijnse, Astrid E.; Peters, Stephan L. M.; Michel, Martin C.

doi:10.1002/nau.20642

Cited by 43 publications

(33 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here we found that the β3-receptor agonist CL316243 caused 14 less relaxation in BOO than in control detrusor. In all, our results are therefore consistent with prior studies (Svalø et al, 2013, Barendrecht et al, 2009 indicating that relaxation to β3-adrenoceptor stimulation is attenuated following outlet obstruction.…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Zeng

Ekman

Jiang

et al. 2015

European Journal of Pharmacology

View full text Add to dashboard Cite

The aim of the present study was to investigate the expression and distribution of membrane receptors after bladder outlet obstruction (BOO). Partial bladder outlet obstruction (BOO) was induced in female rats and bladders were harvested after either 10 days or 6 weeks of BOO. The expression of different receptors was surveyed by microarrays and corroborated by immunohistochemistry and western blotting. A microarray experiment identified 10 membrane receptors that were differentially expressed compared to sham-operated rats including both upregulated and downregulated receptors. Four of these were selected for functional experiments on the basis of magnitude of change and relevance to bladder physiology. At 6 weeks of BOO, maximal contraction was reduced for neuromedin B and vasopressin (AVP), consistent with reductions of receptor mRNA levels. Glycine receptor-induced contraction on the other hand was increased and receptor mRNA expression was accordingly upregulated. Maximal relaxation by the β3-adrenergic receptor agonist CL316243 was reduced as was the receptor mRNA level.Immunohistochemistry supported reduced expression of neuromedin B receptors, V1a receptors and β3-adrenergic receptors, but glycine receptor expression appeared unchanged. Western blotting confirmed repression of V1a receptors and induction of glycine receptors in BOO.mRNA for vasopressin was detectable in the bladder, suggesting local AVP production. We conclude that changes in receptor expression following bladder outlet obstruction are nonuniform. Some receptors are upregulated, conferring increased responsiveness to agonist, whereas others are downregulated, leading to decreased agonist-induced responses. This study might help to select pharmacological agents that are effective in modulating lower urinary tract symptoms in BOO.3

show abstract

Section: Discussionsupporting

confidence: 93%

“…In contrast, Barendrecht et al (2009) did not find any change in β3-adrenoceptor mRNA in bladders from rats with BOO. They had however been obstructed for only 7 days, as compared with 10 days and 6 weeks in the present study.…”

Section: Discussioncontrasting

confidence: 64%

Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Zeng

Ekman

Jiang

et al. 2015

European Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…While we are not aware of β 3 -adrenoceptor mRNA studies on rat or mouse ureter, its expression level in human ureter was reported to be low (Park et al 2000;Matsumoto et al 2013); moreover, in some species including humans, ureter relaxation by β 3 -adrenoceptor agonists has been reported (Park et al 2000;Matsumoto et al 2013). Several studies have reported β 3 -adrenoceptor mRNA in rat bladder, including specifically in its urothelium (Seguchi et al 1998;Fujimura et al 1999;Barendrecht et al 2009;Kullmann et al 2011). While relaxation of rat detrusor strips via β 3 -adrenoceptors has consistently been reported in many studies (Michel and Vrydag 2006;Igawa et al 2012;Michel 2014), we did not detect staining of rat bladder smooth muscle.…”

Section: Discussionmentioning

confidence: 91%

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

Cernecka

Pradidarcheep

Lamers

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

β3-Adrenoceptors play important roles in the regulation of urogenital and probably gastrointestinal function. However, despite recent progress, their detection at the protein level has remained difficult due to a lack of sufficiently validated selective antibodies. Therefore, we have explored the selectivity of two antibodies for the detection of rodent β3-adrenoceptors in immunoblots and immunohistochemistry. Of two reportedly promising candidates, antibody AB15688 did not exhibit subtype selectivity in immunoblots. In contrast, the antibody Sc1473 exhibited at least some selectivity in immunoblots and more promising results in immunocytochemical and immunohistochemical stains in cells transfected with cloned β-adrenoceptor subtypes and in rat and mouse tissues. In a systematic screening of rat gastrointestinal and urogenital tissues, Sc1473 produced selective staining in the epithelial cell lining of the stomach and the urothelium of ureter and bladder. We conclude that the two tested antibodies are inappropriate or at least insufficient for immunoblotting applications, but Sc1473 appears to be useful for immunohistochemical detection of β3-adrenoceptor protein in rodent tissues. The β3-adrenoceptor protein exhibits a distinct expression pattern in the rat gastrointestinal and urogenital tract, which is at least partly in line with previously reported functional data.

show abstract

“…The discrepancies in the reported mRNA and protein expression in the prostate warrant that caution needs to be exercised until additional data are obtained. Human bladder also expresses a 1D -adrenoceptors (Malloy et al, 1998), and both the expression and function increase due to bladder outlet obstruction, both in rats and humans (Hampel et al, 2002;Barendrecht et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

New Multi-target Antagonists of 1A-, 1D-Adrenoceptors and 5-HT1A Receptors Reduce Human Hyperplastic Prostate Cell Growth and the Increase of Intraurethral Pressure

Nascimento-Viana

Carvalho

Nasciutti

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

Benign prostatic hyperplasia (BPH) is characterized by stromal cell proliferation and contraction of the periurethral smooth muscle, causing lower urinary tract symptoms. Current BPH treatment, based on monotherapy with a 1A -adrenoceptor antagonists, is helpful for many patients, but insufficient for others, and recent reports suggest that stimulation of a 1D -adrenoceptors and 5-hydroxytryptamine (serotonin) (5-HT) 1A receptors contributes to cell proliferation. In this study, we investigated the potential of three N-phenylpiperazine derivatives (LDT3, LDT5, and LDT8) as multi-target antagonists of BPH-associated receptors. The affinity and efficacy of LDTs were estimated in isometric contraction and competition-binding assays using tissues (prostate and aorta) and brain membrane samples enriched in specific on-or off-target receptors. LDTs' potency was estimated in intracellular Ca 21 elevation assays using cells overexpressing human a 1 -adrenoceptor subtypes. The antiproliferative effect of LDTs on prostate cells from BPH patients was evaluated by viable cell counting and 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays. We also determined LDTs' effects on rat intraurethral and arterial pressure. LDT3 and LDT5 are potent antagonists of a 1A -, a 1D -adrenoceptors, and 5-HT 1A receptors (K i values in the nanomolar range), and fully inhibited phenylephrine-and 5-HT-induced proliferation of BPH cells. In vivo, LDT3 and LDT5 fully blocked the increase of intraurethral pressure (IUP) induced by phenylephrine at doses (ED 50 of 0.15 and 0.09 mg.kg 21 , respectively) without effect on basal mean blood pressure. LDT3 and LDT5 are multi-target antagonists of key receptors in BPH, and are capable of triggering both prostate muscle relaxation and human hyperplastic prostate cell growth inhibition in vitro. Thus, LDT3 and LDT5 represent potential new lead compounds for BPH treatment.

show abstract

The effect of bladder outlet obstruction on α₁‐ and β‐adrenoceptor expression and function

Cited by 43 publications

References 33 publications

Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

New Multi-target Antagonists of 1A-, 1D-Adrenoceptors and 5-HT1A Receptors Reduce Human Hyperplastic Prostate Cell Growth and the Increase of Intraurethral Pressure

Contact Info

Product

Resources

About

The effect of bladder outlet obstruction on α1‐ and β‐adrenoceptor expression and function

Cited by 43 publications

References 33 publications

Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

New Multi-target Antagonists of 1A-, 1D-Adrenoceptors and 5-HT1A Receptors Reduce Human Hyperplastic Prostate Cell Growth and the Increase of Intraurethral Pressure

Contact Info

Product

Resources

About

The effect of bladder outlet obstruction on α₁‐ and β‐adrenoceptor expression and function