title: Endothelin-1 production and agonist activities in cultured prostate-derived cells: implications for regulation of endothelin bioactivity and bioavailability in prostatic hyperplasia.
abstract: BACKGROUND
  Endothelin-1 (ET-1) interacts with specific G-protein-coupled receptors to initiate short-term (contraction) and long-term (mitogenesis) events in target cells. ET-1 is an abundant prostate secretory protein that, in its biologically active form, elicits prostatic smooth muscle contraction. The present study was designed to determine the effects of ET-1 on prostate cell growth and to examine the regulation of endogenous ET-1 activity and bioavailability.
  
  
  METHODS
  Primary cultures of prostate secretory epithelial (PE) and prostate fibromuscular stromal (PS) cells were established from benign human prostate tissue.
  
  
  RESULTS
  In culture, PE cells secrete immunoreactive ET-1 (38.5 +/- 1.6 pg/ml/10(6) cells/24 hr) into the conditioned medium. Levels of immunoreactive ET-1 produced by PS cells were more than 10-fold lower. Endothelin-converting enzyme-1 (ECE-1) mRNA was detected in PE cells and not in PS cells; however, big ET-1 was the predominant immunoreactive ET-1 secretory product of PE cells. The ET(B) endothelin receptor was the predominant subtype in both PE and PS cells. In PS cells, but not PE cells, ET-1 induced significant inositol phosphate accumulation and [3H]-thymidine uptake. Agonist activity was inhibited by the ET(B) receptor selective antagonist, BQ 788. Intact PE cell monolayers secrete ET-1 through the apical surface, consistent with secretion of ET-1 into the glandular lumen in vivo.
  
  
  CONCLUSIONS
  On the basis of these findings, regulation of ET-1 activity and bioavailability appears to be tightly regulated. Such findings have important implications in the pathophysiology of prostate disease.
authors.affiliation: Department of Urology, NYU Medical Center, New York 10016, USA. paul.walden@nyu.edu
authors.forename: P D
authors.initials: PD
authors.lastname: Walden
authors.forename: M
authors.initials: M
authors.lastname: Ittmann
authors.forename: M E
authors.initials: ME
authors.lastname: Monaco
authors.forename: H
authors.initials: H
authors.lastname: Lepor
mesh_terms: D017209:Apoptosis; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D001682:Biological Availability; D019332:Endothelin-1 / Q000096:biosynthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D019334:Endothelin-3 / Q000032:analysis; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D019332:Endothelin-1; D019334:Endothelin-3; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes