title: Mitogenic actions of endothelin-1 and epidermal growth factor in cultured airway smooth muscle.
abstract: 1. Hyperplasia of airway smooth muscle contributes to the increase in bronchomotor responsiveness that characterizes asthma. We have investigated the mitogenic potential of endothelin-1 (ET-1) and epidermal growth factor (EGF) in guinea-pig cultured airway smooth muscle and the relationship of these actions to tyrosine phosphorylation and increases in intracellular calcium (Ca2+i). 2. ET-1 stimulated DNA and protein synthesis and also increased cell number, but these mitogenic actions were small compared with those of EGF. 3. ET-1 and EGF increased the level of tyrosine phophorylation of a range of proteins with apparent molecular weights between 80 and 100 kDa and also increased phosphorylation of a single protein of 33 kDa. 4. Ca2+i levels were increased by both ET-1 and EGF. However, concentrations of EGF three orders of magnitude higher than those having mitogenic actions or increasing protein tyrosine phosphorylation were required. ET-1 was a more potent stimulant of increases in intracellular calcium than of mitogenesis. 5. We conclude that elevation of Ca2+i is unlikely to be an important signal for the mitogenic action of EGF. It is suggested that stimulants at the EGF receptor (EGF and transforming growth factor alpha) may play a role in the airway smooth muscle hyperplasia in asthma.
authors.affiliation: Microsurgery Research Centre, St Vincent's Hospital, Fitzroy, Victoria, Australia.
authors.forename: A G
authors.initials: AG
authors.lastname: Stewart
authors.forename: G
authors.initials: G
authors.lastname: Grigoriadis
authors.forename: T
authors.initials: T
authors.lastname: Harris
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016232:Endothelins / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D006168:Guinea Pigs; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology* / Q000378:metabolism
chemical_list: D016232:Endothelins; D006133:Growth Substances; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D002118:Calcium