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α1-adrenoceptor act...
α1-adrenoceptor activation induces phosphorylation of β2-adrenoceptors in human prostate tissue
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- Hennenberg, Martin (författare)
- Department of Urology, University of Munich, Munich, Germany
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- Strittmatter, Frank (författare)
- Department of Urology, University of Munich, Munich, Germany
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- Walther, Sebastian (författare)
- Department of Urology, University of Munich, Munich, Germany
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- Hedlund, Petter (författare)
- Urological Research Institute, University of San Raffaele, Milan, Italy
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- Andersson, Karl-Erik (författare)
- Wake Forest Institute for Regenerative Medicine, Wake Forst University School of Medicine, Winston-Salem, NC, USA
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- Stief, Christian G (författare)
- Department of Urology, University of Munich, Munich, Germany
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- Schlenker, Boris (författare)
- Department of Urology, University of Munich, Munich, Germany
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- Gratzke, Christian (författare)
- Department of Urology, University of Munich, Munich, Germany
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(creator_code:org_t)
- 2011
- 2011
- Engelska.
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 108:6, s. 922-928
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- prostate hyperplasia; lower urinary tract symptoms (LUTS); smooth muscle; alphal-adrenoceptor; alphal-blocker; G protein-coupled receptor kinase (GRK)
- MEDICINE
- MEDICIN
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- art (ämneskategori)
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