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01-04-2011 | Original Article

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

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

Published in: World Journal of Urology | Issue 2/2011

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.

Michel MC, Vrydag W (2006) Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol 147(Suppl 2): S88–S119

Roehrborn CG, Schwinn DA (2004) Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol 171(3):1029–1035PubMedCrossRef

Schwinn DA, Roehrborn CG (2008) Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol 15(3):193–199PubMedCrossRef

Andersson KE (2007) LUTS treatment: future treatment options. Neurourol Urodyn 26(6 Suppl):934–947PubMedCrossRef

Christ GJ, Andersson KE (2007) Rho-kinase and effects of Rho-kinase inhibition on the lower urinary tract. Neurourol Urodyn 26(6 Suppl):948–954PubMedCrossRef

Rees RW et al (2003) Y-27632, a Rho-kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cells. J Urol 170(6 Pt 1):2517–2522

Takahashi R et al (2007) RhoA/Rho kinase-mediated Ca2 + sensitization in the contraction of human prostate. Neurourol Urodyn 26(4):547–551PubMedCrossRef

Hennenberg M et al (2008) Mechanisms of extrahepatic vasodilation in portal hypertension. Gut 57(9):1300–1314PubMedCrossRef

Gurevich VV, Gurevich EV, Cleghorn WM (2008) Arrestins as multi-functional signaling adaptors. Handb Exp Pharmacol (186):15–37

10.

Kendall RT, Luttrell LM (2009) Diversity in arrestin function. Cell Mol Life Sci 66(18):2953–2973PubMedCrossRef

11.

Hennenberg M et al (2007) Vascular dysfunction in human and rat cirrhosis: role of receptor-desensitizing and calcium-sensitizing proteins. Hepatology 45(2):495–506PubMedCrossRef

12.

Schmid CL, Bohn LM (2009) Physiological and pharmacological implications of beta-arrestin regulation. Pharmacol Ther 121(3):285–293PubMedCrossRef

13.

Deshpande DA et al (2008) Beta-arrestins specifically constrain beta2-adrenergic receptor signaling and function in airway smooth muscle. FASEB J 22(7):2134–2141PubMedCrossRef

14.

Kohout TA et al (2001) Beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc Natl Acad Sci U S A 98(4):1601–1606PubMedCrossRef

15.

Hennenberg M et al (2009) Vascular hyporesponsiveness to angiotensin II in rats with CCl(4)-induced liver cirrhosis. Eur J Clin Invest 39(10):906–913PubMedCrossRef

16.

Lakshmikanthan V et al (2009) Identification of beta-arrestin2 as a corepressor of androgen receptor signaling in prostate cancer. Proc Natl Acad Sci U S A 106(23):9379–9384PubMedCrossRef

17.

Yassin A et al (2006) Alpha-adrenoceptors are a common denominator in the pathophysiology of erectile function and BPH/LUTS–implications for clinical practice. Andrologia 38(1):1–12PubMedCrossRef

18.

Brown MD, Sacks DB (2009) Protein scaffolds in MAP kinase signalling. Cell Signal 21(4):462–469PubMedCrossRef

19.

Anglin IE, Glassman DT, Kyprianou N (2002) Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis 5(2):88–95PubMedCrossRef

20.

Golomb E et al (1998) Induction of atypical prostatic hyperplasia in rats by sympathomimetic stimulation. Prostate 34(3):214–221PubMedCrossRef

21.

Kyprianou N (2003) Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance. J Urol 169(4):1520–1525PubMedCrossRef

22.

Kyprianou N, Jacobs SC (2000) Induction of apoptosis in the prostate by alpha1-adrenoceptor antagonists: a novel effect of “old” drugs. Curr Urol Rep 1(2):89–96PubMedCrossRef

23.

Marinese D, Patel R, Walden PD (2003) Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice. Prostate 54(3):230–237PubMedCrossRef

24.

McVary KT et al (1994) Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod 51(1):99–107PubMedCrossRef

Title: Beta-arrestin-2 is expressed in human prostate smooth muscle and a binding partner of α1A-adrenoceptors
Authors: Martin Hennenberg
Boris Schlenker
Alexander Roosen
Frank Strittmatter
Sebastian Walther
Christian Stief
Christian Gratzke
Publication date: 01-04-2011
Publisher: Springer-Verlag
Published in: World Journal of Urology / Issue 2/2011
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-010-0634-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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