Effects of alpha I-adrenoceptor antagonists on cultured prostatic smooth muscle cells

BACKGROUND. alpha1-adrenoceptor (alpha1-AR) antagonists, used to relieve th e lower tract urinary symptoms (LUTS) in benign prostate hyperplasia (BPH) patients, are thought to act in inhibiting the contraction of stromal smoot h muscle. An attempt was made using new technology to visualize and quantif y the effect of alpha1-AR antagonists in a cell culture model of prostatic smooth muscle cells (SMC). METHODS. Prostatic smooth muscle cells cultured from human prostate tissue were treated with alpha1-AR agonists and antagonists. The effects on cell g rowth, cell contraction, differentiation status, and apoptosis were determi ned by means of an MTT cell viability assay, time-lapse video microscopy, R T-PCR analysis, and FACS analysis of annexin V/propidium iodide-stained cel ls, respectively. RESULTS. Prostatic smooth muscle cells derived from prostate tissue express ed SMC-specific markers. They showed spontaneous contractions, and phenylep hrine increased the percentage of contracting cells by 3-fold. alpha1-AR an tagonists inhibited spontaneous as well as phenylephrine-induced contractio ns. Long-term treatment with doxazosin induced differentiation tended towar ds a contractile phenotype, as indicated by an increase of the ratio of smo oth muscle heavy chain myosin subtypes SM2/SM1. There was, however, no effe ct on cell growth. High concentrations of antagonist (100 muM) induced apop tosis in about 80% of the treated SMC. This effect was not cell-type-specif ic and was also seen in skin fibroblasts and immortalized prostate epitheli al cells. CONCLUSION. In an easy-to-handle cell culture model of prostatic smooth mus cle cells, the effects of alpha1-AR antagonists on cell contraction, growth , and differentiation can be investigated. The results indicate that in add ition to inhibition of cell contraction, alpha1-AR antagonists have the pot ential to induce apoptosis. Prostate Supplement 9:34-41, 2000. (C) 2000 Wil ey-Liss, Inc.