Mitogenic actions of endothelin-1 and epidermal growth factor in cultured airway smooth muscle

Alastair G Stewart, George Grigoriadis, Trudi Harris

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Abstract

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)). ET-1 stimulated DNA and protein synthesis and also increased cell number, but these mitogenic actions were small compared with those of EGF. ET-1 and EGF increased the level of tyrosine phosphorylation 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. 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. 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 a) may play a role in the airway smooth muscle hyperplasia in asthma.
Original languageEnglish
Pages (from-to)277 - 285
Number of pages9
JournalClinical and Experimental Pharmacology and Physiology
Volume21
Issue number4
DOIs
Publication statusPublished - 1994

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