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

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 M) on p38 activity was assessed by Western blot analysis with a phosphospecific antibody. Expression of p38 was studied by immunohistochemistry and immunofluorescence staining. The effect of the p38 inhibitor SB 202190 (10 M) 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 1adrenergic contraction, and points to 1-adrenoceptor functions beyond contraction. UROLOGY 78: 969.e7‐969.e13, 2011. © 2011 Elsevier Inc.