Mitogenic activity of endothelin on human cultured prostatic smooth muscle cells

The effects of endothelins on human prostatic smooth-muscle cell growth were examined. Endothelin-1 and endothelin-3 induced a concentration-dependent increase in DNA synthesis and also promoted cell growth. Use of subtype selective antagonists BQ-123 ((cyclo(D-Trp-D-Asp(ONa)-Pro-D-Val-Leu); endothelin ETA receptor selective) and BQ788 ((N-cis-2,6-dimethylpiperidinocarbonyl-L -gamma-methyl Leu-D-Trp-(COOMe)-D-Nle-ONa); endothelin ETB receptor selective), indicated that mitogenic effects of endothelin were mediated through activation of both endothelin ETA and ET(B )receptors. The mitogenic effects of endothelin-1 and endothelin-3 were significantly inhibited by pretreatment of the cells with pertussis toxin. However, mitogenesis due to basic fibroblast growth factor was not affected. In conclusion, endothelin has mitogenic effects on human prostatic smooth muscle cells through activation of both endothelin ETA and ETB receptors via different signalling pathways from basic fibroblast growth factor. This may contribute to smooth muscle hyperplasia associated with benign prostatic hyperplasia. (C) 1998 Elsevier Science B.V. All rights reserved.