title: Endothelin-1 activation of ETB receptors leads to a reduced cellular proliferative rate and an increased cellular footprint.
abstract: Endothelin-1 (ET-1) is a vasoactive peptide which signals through two G-protein coupled receptors, endothelin receptor A (ETA) and B (ETB). We determined that ET-1 activation of its ETB receptor in stably cDNA transfected CHO cells leads to a 55% reduction in cell number by end-point cell counting and a 35% decrease in cell growth by a real-time cell-substrate impedance-based assay after 24h of cell growth. When CHO ETB cells were synchronized in the late G1 cell cycle phase, ET-1 delayed their S phase progression compared to control by 30% as determined by [(3)H]-thymidine incorporation. On the other hand, no such delay was observed during late G2/M to G1 transit when cells were treated with ET-1 after release from mitotic arrest. Using the cell-substrate impedance-based assay, we observed that ET-1 induces opposing morphological changes in CHO ETA and CHO ETB cells with ETB causing an increase in the cell footprint and ETA a decrease. Likewise, in pulmonary artery smooth muscle cells, which express both ETA and ETB receptors, ET-1 induces an ETA-dependent contraction and an ETB dependent dilation. These results are shedding light on a possible beneficial role for ETB in diseases involving ET-1 dysfunction such as pulmonary hypertension.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, 72 E. Concord Street, Boston, MA 02118, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Wilson
authors.forename: Linda
authors.initials: L
authors.lastname: Taylor
authors.forename: Peter
authors.initials: P
authors.lastname: Polgar
mesh_terms: D000818:Animals; D016466:CHO Cells; D002452:Cell Count; D002453:Cell Cycle; D049109:Cell Proliferation; D048430:Cell Shape / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D017097:Electric Impedance; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; D004247:DNA