α1-adrenoceptor activation induces phosphorylation of β2-adrenoceptors in human prostate tissue

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α1-adrenoceptor activation induces phosphorylation of β2-adrenoceptors in human prostate tissue

Hennenberg, Martin (author): Department of Urology, University of Munich, Munich, Germany

Strittmatter, Frank (author): Department of Urology, University of Munich, Munich, Germany

Walther, Sebastian (author): Department of Urology, University of Munich, Munich, Germany

Hedlund, Petter (author): Urological Research Institute, University of San Raffaele, Milan, Italy

Andersson, Karl-Erik (author): Wake Forest Institute for Regenerative Medicine, Wake Forst University School of Medicine, Winston-Salem, NC, USA

Stief, Christian G (author): Department of Urology, University of Munich, Munich, Germany

Schlenker, Boris (author): Department of Urology, University of Munich, Munich, Germany

Gratzke, Christian (author): Department of Urology, University of Munich, Munich, Germany

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(creator_code:org_t)

2011
2011
English.
In: BJU International. - 1464-4096 .- 1464-410X. ; 108:6, s. 922-928

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

OBJECTIVE:• To test whether β1-adrenoceptor activation leads to phosphorylation of the β2-adrenoceptor in human prostate tissue.PATIENTS AND METHODS:• Prostate tissue from patients undergoing radical prostatectomy was stimulated in vitro with the α1-adrenergic agonist phenylephrine (10 µM).• α2-adrenoceptor phosphorylation at serines 345/346 was studied using Western blot analysis with a phospho-specific antibody.• The role of second messenger kinases was assessed by studying the effects of the protein kinase C (PKC) inhibitor Ro 31-8425 and the protein kinase A (PKA) inhibitor H89 on phenylephrine-induced phosphorylation.• The expression of G protein-coupled receptor kinases (GRKs) 2/3 was analysed using quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry.RESULTS:• Stimulation of prostate tissue with phenylephrine resulted in phosphorylation of the β2-adrenoceptor (5, 10 and 20 min after stimulation).• This α1-adrenoceptor-induced phosphorylation of β2-adrenoceptors was resistant to inhibition of PKC and PKA.• Changes in phosphorylation levels were not attributable to changes in receptor levels, as these remained constant during stimulation.• RT-PCR and Western blot analysis showed expression of GRK2/3 in human prostate tissues.• Immunohistochemical staining showed that GRK2/3 expression in human prostate tissue is located to stromal and smooth muscle cells.CONCLUSIONS:• Activation of α1-adrenoceptors causes phosphorylation of β2-adrenoceptors in the human prostate. This may enhance α1-adrenergic contraction and is possibly mediated by GRK2, which is expressed in prostate smooth muscle.• Mutual regulation between different adrenergic receptors might be involved in the therapeutic effects of α1-blockers in patients with benign prostate hyperplasia.

Keyword

prostate hyperplasia; lower urinary tract symptoms (LUTS); smooth muscle; alphal-adrenoceptor; alphal-blocker; G protein-coupled receptor kinase (GRK)
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By the author/editor: Hennenberg, Mart ...; Strittmatter, Fr ...; Walther, Sebasti ...; Hedlund, Petter; Andersson, Karl- ...; Stief, Christian ...; show more...; Schlenker, Boris; Gratzke, Christi ...; show less...

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By the university: Linköping University

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