TY - JOUR
T1 - ET-1 induces mitogenesis in ovine airway smooth muscle cells via ET(A) and ET(B) receptors
AU - Carratu, Pierluigu
AU - Scuri, Mario
AU - Styblo, James L.
AU - Wanner, Adam
AU - Glassberg, Marilyn K.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1997/5
Y1 - 1997/5
N2 - The proliferation of airway smooth muscle cells is a characteristic feature of asthma. Endothelin (ET)-1, a member of a family of three isopeptides (ET-1, ET-2, and ET-3), functions as a spasmogen and mitogen for airway smooth muscle cells. Two types of ET receptors have been identified in mammalian species (ET(A) and ET(B)). Because the respective roles of ET(A) and ET(B) receptors in ET-1-induced mitogenesis are not known, we determined the effect of two selective ET(A) and ET(B) antagonists (BQ-610 and BQ-788) on ET-1-induced mitogenesis of cultured ovine airway smooth muscle cells. Both BQ-610 and BQ-788 inhibited ET-1-induced mitogenesis in a concentration- dependent manner, with BQ-788 exhibiting more potent antagonism [half- maximal inhibitory concentration (IC50) = 3.5 nM, slope of 0.49] compared with BQ-610 (IC50 = 20 nM, slope of 0.27). The combined ET(A)-ET(B) antagonist, bosentan, also inhibited ET-1-induced mitogenesis (IC50 = 20 nM, slope of 0.60). The effects of BQ-788 and bosentan appear to be mediated via the same receptor (ET(B)), as their slopes are comparable. These observations suggest that both receptor subtypes are utilized in ET-1- induced proliferation of ovine airway smooth muscle. ET receptor expression may be important in the increase in airway smooth muscle mass seen in the airways of patients with bronchial asthma.
AB - The proliferation of airway smooth muscle cells is a characteristic feature of asthma. Endothelin (ET)-1, a member of a family of three isopeptides (ET-1, ET-2, and ET-3), functions as a spasmogen and mitogen for airway smooth muscle cells. Two types of ET receptors have been identified in mammalian species (ET(A) and ET(B)). Because the respective roles of ET(A) and ET(B) receptors in ET-1-induced mitogenesis are not known, we determined the effect of two selective ET(A) and ET(B) antagonists (BQ-610 and BQ-788) on ET-1-induced mitogenesis of cultured ovine airway smooth muscle cells. Both BQ-610 and BQ-788 inhibited ET-1-induced mitogenesis in a concentration- dependent manner, with BQ-788 exhibiting more potent antagonism [half- maximal inhibitory concentration (IC50) = 3.5 nM, slope of 0.49] compared with BQ-610 (IC50 = 20 nM, slope of 0.27). The combined ET(A)-ET(B) antagonist, bosentan, also inhibited ET-1-induced mitogenesis (IC50 = 20 nM, slope of 0.60). The effects of BQ-788 and bosentan appear to be mediated via the same receptor (ET(B)), as their slopes are comparable. These observations suggest that both receptor subtypes are utilized in ET-1- induced proliferation of ovine airway smooth muscle. ET receptor expression may be important in the increase in airway smooth muscle mass seen in the airways of patients with bronchial asthma.
KW - Endothelin
KW - Endothelin receptors
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U2 - 10.1152/ajplung.1997.272.5.l1021
DO - 10.1152/ajplung.1997.272.5.l1021
M3 - Article
C2 - 9176269
AN - SCOPUS:0030980907
VL - 272
SP - L1021-L1024
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 5 16-5
ER -