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 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.

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 α-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 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.