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 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.
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki, Japan. saita@yamanouchi.co.jp
Y
Y
Saita
H
H
Yazawa
T
T
Koizumi
T
T
Morita
T
T
Tamura
T
T
Takenaka
K
K
Honda
D000368:Aged; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology; D019334:Endothelin-3 / Q000494:pharmacology / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008297:Male; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects; D037342:Pertussis Toxin; D011467:Prostate / Q000166:cytology* / Q000187:drug effects; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D010566:Virulence Factors, Bordetella; D016222:Fibroblast Growth Factor 2; D004247:DNA; D037342:Pertussis Toxin