Alpha1-adrenoceptor Signaling in the Human Prostate Involves Regulation of p38 Mitogen-activated Protein Kinase - 07/10/11
Résumé |
Objective |
To investigate whether 1-adrenoceptor signaling in the human prostate involves regulation of the mitogen-activated protein kinase (MAPK) p38. Although ⍺1-adrenoceptors are an important target for therapy of lower urinary tract symptoms in patients with prostate hyperplasia, intracellular signaling by prostate ⍺1-adrenoceptors is not sufficiently understood.
Methods |
Prostate tissue was obtained from patients undergoing radical prostatectomy. The effect of phenylephrine (10 μM) on p38 activity was assessed by Western blot analysis with a phospho-specific antibody. Expression of p38 was studied by immunohistochemistry and immunofluorescence staining. The effect of the p38 inhibitor SB 202190 (10 μM) on phenylephrine-induced contraction was studied in myographic measurements.
Results |
Stimulation of human prostate tissue with phenylephrine resulted in reduced threonine180/tyrosine182 phosphorylation of p38, indicating deactivation of p38 (P = .039 after 5 minutes). Immunohistochemical staining demonstrated expression of p38 in stromal cells of human prostate tissue. Immunofluorescence staining identified these cells as smooth muscle cells, as p38 colocalized with immunoreactivity for ⍺-smooth muscle actin.
The p38 inhibitor SB 202190 was without effect on phenylephrine-induced contraction.
Conclusion |
Using intact human prostate tissue, we herewith describe a new signal transduction pathway of prostate ⍺1-adrenoceptors. In addition to mediating contraction, prostate ⍺1-adrenoceptors induce intracellular signaling, which results in deactivation of p38 MAPK. This is not involved in ⍺1-adrenergic contraction, and points to ⍺1-adrenoceptor functions beyond contraction.
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Funding Support: 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). |
Vol 78 - N° 4
P. 969.e7-969.e13 - octobre 2011 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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