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Beta-arrestin-2 is expressed in human prostate smooth muscle and a binding partner of α1A-adrenoceptors

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Abstract

Purpose

Alpha1A-adrenoceptors are important regulators of prostatic smooth muscle tone and an important target for therapy of lower urinary tract symptoms. The function of heptahelical transmembrane receptors such as adrenoceptors can be regulated by β-arrestin-2, which may bind to receptors besides G proteins. Here, we investigated the expression and α1A-adrenoceptor binding of β-arrestin-2 in the human prostate.

Methods

Human prostatic tissues were obtained from patients undergoing radical prostatectomies. The expression of β-arrestin-2 and α1A-adrenoceptors was studied by RT–PCR, Western blot analysis, and immunohistochemistry. The protein–protein interaction between α1A-adrenoceptors and β-arrestin-2 was investigated by coimmunoprecipitation.

Results

RT–PCR and Western blot analysis demonstrated the expression of β-arrestin-2 mRNA and protein in the human prostate. Immunohistochemistry demonstrated β-arrestin-2 expression in smooth muscle and stromal cells. Coimmunoprecipitation studies demonstrated that α1A-adrenoceptors in the human prostate may interact with β-arrestin-2. Thus, specific binding of β-arrestin-2 to α1A-adrenoceptors was significantly higher than background during α1A-adrenoceptor detection in β-arrestin-2 precipitates (P < 0.001) or during β-arrestin-2 detection in α1A-adrenoceptor precipitates (P < 0.005). This interaction may be located to prostate smooth muscle cells, as expression of the α1A-adrenoceptor was exclusively found in smooth muscle cells after immunohistochemical staining.

Conclusion

With β-arrestin-2, we identified a new binding partner of the α1A-adrenoceptor in human prostate smooth muscle. Binding of β-arrestin-2 may be involved in posttranslational regulation of prostate α1A-adrenoceptors.

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Abbreviations

BPH:

Benign prostate hyperplasia

cDNA:

Copy desoxyribonucleic acid

Ct:

Number of cycles

IP3 :

Inositol-1,4,5-trisphosphate

LUT:

Lower urinary tract

LUTS:

Lower urinary tract symptoms

mRNA:

Messenger ribonucleic acid

PBS:

Phosphate-buffered saline

RNA:

Ribonucleic acid

RT–PCR:

Real-time polymerase chain reaction

SEM:

Standard error of the mean

SDS:

Sodium dodecyl sulfate

18SrRNA:

Eucaryotic small subunit ribosomal ribonucleic acid

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Acknowledgments

We thank B. Rutz, M. Perutka, and B. Stadlbauer for excellent technical assistance. This study was supported by grants of the “Förderprogramm für Forschung und Lehre” (FöFoLe) of the Ludwig-Maximilians university, Munich, Germany (grant Reg.-Nr. 654).

Conflict of Interest

None.

Author information

Authors and Affiliations

  1. Department of Urology, Ludwig-Maximilians University, Munich, Germany

    Martin Hennenberg, Boris Schlenker, Alexander Roosen, Frank Strittmatter, Sebastian Walther, Christian Stief & Christian Gratzke

  2. Urologische Klinik, Universitäts-Klinikum Großhadern, Marchioninistr. 15, 81377, Munich, Germany

    Christian Gratzke

Authors
  1. Martin Hennenberg
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  2. Boris Schlenker
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  3. Alexander Roosen
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  4. Frank Strittmatter
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  5. Sebastian Walther
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  6. Christian Stief
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  7. Christian Gratzke
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Correspondence to Christian Gratzke.

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Hennenberg, M., Schlenker, B., Roosen, A. et al. Beta-arrestin-2 is expressed in human prostate smooth muscle and a binding partner of α1A-adrenoceptors. World J Urol 29, 157–163 (2011). https://doi.org/10.1007/s00345-010-0634-3

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  • DOI: https://doi.org/10.1007/s00345-010-0634-3

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