Phosphoramidon and thiorphan suppress the generation of endothelin (ET) from exogenous big-endothelin by guinea pig Clara cells

Content Provider	Semantic Scholar
Author	Laporte, Johanne Sirois, Pierre
Copyright Year	1997
Abstract	The formation of endothelins (ET) from exogenous big-ET-1, -2 and -3 was investigated in cultured guinea pig Clara cells. When Clara cells were incubated with 10(-9) or 10(-8) M human big-ET-1 (1-38), the release of ET was 69.9 +/- 7.6 and 221.6 +/- 25 fmol/ml respectively, after 1 h incubation period. Treatment of Clara cells with 1 mM phosphoramidon strongly suppressed (80%) the conversion of big-ET-1 to ET-1 during 1, 2 and 6 h incubation periods. Treatment of Clara cells with thiorphan (1 mM), an inhibitor of neutral endopeptidase, decreased by 44 and 26% the levels of immunoreactive endothelin (ir-ET) in the cell supernatant respectively, after 1 and 2 h incubation periods. When Clara cells were incubated with 10(-8) M human big-ET-2 (1-38), the release of ir-ET was 287.6 +/- 8.9 fmol/ml after a 1 h incubation period. Phosphoramidon and thiorphan (1 mM) reduced the amount of ir-ET generated from exogenous human big-ET-2 (10(-8) M) by 69 and 56%, respectively. When Clara cells were incubated with 10(-8) M human big-ET-3 (1-41), the release of ET was not increased after a 1 h incubation period. Our results suggest that guinea pig Clara cells convert exogenous big-ET-1 and -2 but not big-ET-3 into ET-1 and ET-2, respectively, through metalloproteinases sensitive to both phosphoramidon and thiorphan.
Starting Page	105
Ending Page	109
Page Count	5
File Format	PDF HTM / HTML
DOI	10.1016/S0167-0115(96)02111-8
PubMed reference number	9110381
Journal	Medline
Volume Number	68
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S0167011596021118
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S0167011596021118?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1016/S0167-0115%2896%2902111-8
Journal	Regulatory Peptides
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article