Saita Y, Yazawa H, Koizumi T, Morita T, Tamura T, Takenaka T, Honda K
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki, Japan.
Eur J Pharmacol. 1998 May 15;349(1):123-8. doi: 10.1016/s0014-2999(98)00183-6.
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 ET(A) receptor selective) and BQ-788 ((N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl Leu-D-Trp-(COOMe)-D-Nle-ONa); endothelin ET(B) receptor selective), indicated that mitogenic effects of endothelin were mediated through activation of both endothelin ET(A) 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 ET(A) and ET(B) receptors via different signalling pathways from basic fibroblast growth factor. This may contribute to smooth muscle hyperplasia associated with benign prostatic hyperplasia.
研究了内皮素对人前列腺平滑肌细胞生长的影响。内皮素-1和内皮素-3可诱导DNA合成呈浓度依赖性增加，并促进细胞生长。使用亚型选择性拮抗剂BQ-123（环（D-色氨酸-D-天冬氨酸（ONa）-脯氨酸-D-缬氨酸-亮氨酸）；内皮素ET(A)受体选择性）和BQ-788（N-顺式-2,6-二甲基哌啶羰基-L-γ-甲基亮氨酸-D-色氨酸-（COOMe）-D-正亮氨酸-ONa；内皮素ET(B)受体选择性）表明，内皮素的促有丝分裂作用是通过激活内皮素ET(A)和ET(B)受体介导的。用百日咳毒素预处理细胞可显著抑制内皮素-1和内皮素-3的促有丝分裂作用。然而，碱性成纤维细胞生长因子引起的有丝分裂不受影响。总之，内皮素通过激活内皮素ET(A)和ET(B)受体，通过与碱性成纤维细胞生长因子不同的信号通路，对人前列腺平滑肌细胞具有促有丝分裂作用。这可能导致与良性前列腺增生相关的平滑肌增生。
