title: Endothelin receptor in benign prostatic hyperplastic cells. Binding and functional studies.
abstract: Endothelins (ETs) are 21-amino acid peptides that bind to membrane receptors to initiate pathophysiological effects. This report characterizes ET receptors in benign prostatic hyperplasia-1 (BPH-1) cells, a prostate cell line isolated from a specimen of a 60-yr-old man with benign prostatic hyperplasia. [(125)I]ET-1 or -3 binding was of high affinity, with B(max) and K(d) values of 48 fmol/1 x 10(6) cells and 0.16 nM for ET-1, and 2.9 fmol/1 x 10(6) cells and 0.033 nM for ET-3, respectively. ET-1, ET-3, FR139317, Ro 46-2005, and IRL1620 inhibited [(125)I]ET-1 binding to these cells with IC50 values of 0.22, 186, 0.20, 52.8, and 772.3 nM, respectively. Reverse transcription-polymerase chain reaction confirmed that BPH-1 cells expressed more ET(A) than ET(B) receptors. ET-1 did not have any effect on arachidonic acid release, but caused a modest stimulation of phosphatidylinositol hydrolysis, and induced a prominent, sustained elevation in intracellular Ca2+ concentrations. The functional effects of ET-1 were completely inhibited by the ET(A)-selective antagonists FR139317 and A-127722, suggesting that the effects were mediated by the ET(A) receptor. These results suggest that ET may play functional roles in benign prostatic hyperplasia.
authors.affiliation: Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Wu-Wong
authors.forename: W J
authors.initials: WJ
authors.lastname: Chiou
authors.forename: B
authors.initials: B
authors.lastname: Saeed
authors.forename: S R
authors.initials: SR
authors.lastname: Magnuson
authors.forename: B D
authors.initials: BD
authors.lastname: Dayton
authors.forename: S C
authors.initials: SC
authors.lastname: Ng
authors.forename: T J
authors.initials: TJ
authors.lastname: Opgenorth
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D010716:Phosphatidylinositols / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D019332:Endothelin-1; D010716:Phosphatidylinositols; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016718:Arachidonic Acid; D002118:Calcium