Alpha1-adrenoceptor Signaling in the Human Prostate Involves Regulation of p38 Mitogen-activated Protein Kinase

Abstract

To investigate whether 1-adrenoceptor signaling in the human prostate involves regulation of the mitogen-activated protein kinase (MAPK) p38. Although α1-adrenoceptors are an important target for therapy of lower urinary tract symptoms in patients with prostate hyperplasia, intracellular signaling by prostate α1-adrenoceptors is not sufficiently understood. 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. 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 α-smooth muscle actin. The p38 inhibitor SB 202190 was without effect on phenylephrine-induced contraction. Using intact human prostate tissue, we herewith describe a new signal transduction pathway of prostate α1-adrenoceptors. In addition to mediating contraction, prostate α1-adrenoceptors induce intracellular signaling, which results in deactivation of p38 MAPK. This is not involved in α1-adrenergic contraction, and points to α1-adrenoceptor functions beyond contraction.