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


CONCLUSIONS
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.
Department of Urology, Ludwig-Maximilians University, Munich, Germany.
Martin
M
Hennenberg
Boris
B
Schlenker
Alexander
A
Roosen
Frank
F
Strittmatter
Sebastian
S
Walther
Christian
C
Stief
Christian
C
Gratzke
D019390:Arrestins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605254:ARRB2 protein, human; D019390:Arrestins; D018340:Receptors, Adrenergic, alpha-1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
Int J Urol. 2008 Mar;15(3):193-9
18304211
Eur J Clin Invest. 2009 Oct;39(10):906-13
19522833
Cell Signal. 2009 Apr;21(4):462-9
19091303
J Urol. 2003 Apr;169(4):1520-5
12629407
J Urol. 2004 Mar;171(3):1029-35
14767264
Hepatology. 2007 Feb;45(2):495-506
17256744
Prostate Cancer Prostatic Dis. 2002;5(2):88-95
12496995
Andrologia. 2006 Feb;38(1):1-12
16420236
Gut. 2008 Sep;57(9):1300-14
18445644
Neurourol Urodyn. 2007;26(4):547-551
17304522
Handb Exp Pharmacol. 2008;(186):15-37
18491047
Neurourol Urodyn. 2007 Oct;26(6 Suppl):934-47
17696154
Pharmacol Ther. 2009 Mar;121(3):285-93
19100766
FASEB J. 2008 Jul;22(7):2134-41
18337459
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9379-84
19458261
Br J Pharmacol. 2006 Feb;147 Suppl 2:S88-119
16465187
J Urol. 2003 Dec;170(6 Pt 1):2517-22
14634463
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1601-6
11171997
Curr Urol Rep. 2000 Aug;1(2):89-96
12084321
Biol Reprod. 1994 Jul;51(1):99-107
7918880
Prostate. 1998 Feb 15;34(3):214-21
9492850
Prostate. 2003 Feb 15;54(3):230-7
12518328
Cell Mol Life Sci. 2009 Sep;66(18):2953-73
19597700
Neurourol Urodyn. 2007 Oct;26(6 Suppl):948-54
17696159