Evidence for signalling by big endothelin-1 via conversion to endothelin-1 in pulmonary artery smooth muscle cells.
In this study, signalling by big endothelin-1 (big ET-1) and a role for the phosphoramidon-sensitive endothelin converting enzyme in this signalling was investigated in smooth muscle cells cultured from bovine pulmonary artery. In whole cells, both ET-1 and big ET-1 stimulated inositol phosphate accumulation in a time- and concentration-dependent manner. The endothelin ET-A receptor antagonist (BQ 123, 1 microM) significantly inhibited stimulation by ET-1 (10 nM) or big ET-1 (100 nM). When cells were pretreated with 100 microM phosphoramidon, the stimulation by big ET-1, but not ET-1 was abolished. In separate experiments, when cells were incubated with exogenous big ET-1, a time-dependent phosphoramidon-sensitive conversion to ET-1 was detected by radioimmunoassay. These results are consistent with the presence of a phosphoramidon-sensitive endothelin converting enzyme on the surface of bovine pulmonary artery smooth muscle cells, which may play a role in regulating signalling by circulating big ET-1.
Kent
A
A
Department of Pharmacology, University College, Belfield, Dublin, Ireland.
Keenan
A K
AK
D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019332:Endothelin-1; D016232:Endothelins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011651:Pulmonary Artery; D011863:Radioimmunoassay; D015398:Signal Transduction; D013997:Time Factors
D019332:Endothelin-1; D016232:Endothelins; D010716:Phosphatidylinositols; D011498:Protein Precursors